Neurotransmitters of Autonomic Nervous System

Abstract

Autonomic nervous system (ANS) regulates the physiologic process in the body and has essential role in the systems such as blood pressure regulation, respiration, heart rate, and sexual arousal. ANS is divided into the sympathetic nervous system and the parasympathetic nervous system and regulates whole organism functions in the body. Although the main neurotransmitters in the ANS are norephinephrine, epinephrine, and acetilcholine, many other different agents and chemicals play an important role of the neurotransmitters function. These molecules act on many different receptors and sides. This chapter provides a detailed evaluation of neurotransmitters, related molecules, their receptors and how they function to maintain autonomic functions in both the central and peripheral parts of the systems.

1. Introduction

The autonomic nervous system (ANS) is a complex network of nerves responsible for regulating involuntary body functions such as heart rate, blood pressure, bladder function, digestion, and respiration. The ANS is divided into two main branches: the sympathetic nervous system and the parasympathetic nervous system, both of which use different neurotransmitters to carry out their functions. The sympathetic nervous system is responsible for initiating the “fight or flight” response by increasing heart rate and blood pressure, dilating the pupils, and redirecting blood flow from the digestive system to the muscles. This reaction is triggered in response to perceived threats and prepares the body for action. Conversely, the parasympathetic nervous system slows the heart rate and respiration, constricts the pupils, and increases blood flow to the digestive system. This results in a “rest and digest” response, that promotes relaxation and facilitates recovery from stress. The ANS is critical to maintaining homeostasis by balancing body functions and adapting to changes in the environment. It regulates several vital activities that are important for survival and helps us respond appropriately to different situations [1].

Neurotransmitters are the crucial mediators of interneuronal communication, responsible for transmitting signals between neurons and their target cells. On the website ANS, several neurotransmitters have been discovered, each with unique functions and roles, including acetylcholine, norepinephrine, dopamine, serotonin, and neuropeptides [1]. In recent years, numerous neurotransmitters have been discovered to be involved in signal transduction, revealing the complicated and multifaceted nature of autonomic regulation. This chapter will review some of the recent discoveries in this field and highlight the functions and mechanisms of action of some important neurotransmitters.

Recent discoveries have shown that the ANS is organized in complex ways and that the function and structure of non-synaptic autonomic neuroeffectors is a crucial aspect of ANS regulation. In addition to classical neurotransmission, the concept of co-transmission has been introduced, in which multiple neurotransmitters can be released from a single neuron [2]. In addition, neuromodulation is another important concept in neuroscience that has contributed significantly to our understanding of ANS. Neuromodulators are chemicals that alter the activity of neurotransmitters and their receptors, thereby modulating the strength and efficacy of synaptic transmission [3]. Both co-transmission and neuromodulation are essential for the flexible and dynamic regulation of physiological processes and enable ANS to respond rapidly and appropriately to changes in the internal and external environment [2, 3]. Thanks to advances in molecular biology and imaging techniques, we can study these processes in great detail and gain insight into the complex mechanisms underlying autonomic neurotransmission.

2. Neuroeffector junction

The autonomic neuromuscular junction (ANMJ) is a specialized synapse where autonomic nerve impulses are transmitted to effector cells such as smooth muscle, cardiac muscle, and glands. Unlike the skeletal neuromuscular junction, the ANMJ lacks pre- and post-functional specialization. It has varicosities that release neurotransmitters during impulse transmission [4]. The structure of the ANMJ may vary depending on the type of effector cell. In smooth muscle cells, neuromuscular junctions are diffuse and distributed over a large area. In cardiac muscle cells, the neuromuscular junctions are located in the intercalated discs between adjacent cells. In glandular cells, the neuromuscular junction sites are located at the cell membrane. The ANMJ facilitates the transmission of nerve impulses through the release of neurotransmitters from the presynaptic neuron, the diffusion of these neurotransmitters across the synaptic cleft, and the activation of post-synaptic receptors on the effector cell. Acetylcholine and norepinephrine are the two major neurotransmitters involved in ANMJ [1, 5]. Acetylcholine is the neurotransmitter released by both preganglionic and post-ganglionic neurons of the parasympathetic division. It acts on muscarinic receptors in effector cells and causes smooth muscle cell contraction, slowing of heart rate in cardiac myocytes, and secretion of glandular cells [6]. In the sympathetic nervous system, norepinephrine is the neurotransmitter released by post-ganglionic neurons. Norepinephrine acts on alpha- and beta-adrenergic receptors in effector cells and leads to contraction of smooth muscle cells, acceleration of heart rate in cardiac muscle cells, and secretion of glandular cells [7].

The ANMJ effectors are muscle bundles connected by low-resistance pathways that allow electrotonic propagation of activity within the smooth muscle bundle. Varicosities are constantly in motion and have a dynamic relationship with muscle cell membranes, which means that a given impulse is likely to trigger transmitter release from only some of the varicosities it encounters. In addition, neurotransmitters such as dopamine, serotonin, and histamine may also be released at the ANMJ and modulate its activity. In addition, other substances such as hormones, locally released agents, and neurotransmitters from nearby nerves can also alter neurotransmission by affecting either the release or the action of the transmitter. Many of these substances, including co-transmitters, are capable of affecting neuronal growth and development. Because the autonomic neuroeffector junctions have a wide and variable gap, they are particularly suitable for the above mechanisms of neuronal control [8].

3. Signaling molecules and their receptors

Neurotransmitters are molecules released by nerves in response to electrical stimulation that bind to specific receptors on neighboring cells to produce a response. For a substance to be classified as a neurotransmitter, it must meet certain criteria, such as being synthesized and stored by the presynaptic neuron, being released in a calcium-dependent manner, having a mechanism to terminate release, and producing effects similar to those of electrical nerve stimulation when applied locally [9]. Although early studies identified only a few neurotransmitters in the ANS, more recent research has identified several substances, such as monoamines, amino acids, neuropeptides, ATP, nitric oxide (NO), and carbon monoxide (CO) [10, 11].

Neurons can store and release various neurotransmitters and neuromodulators that can have different effects on target cells. Neurons can have both slow-acting neuropeptide transmitters and fast-acting small molecule transmitters that can be present in the same neurons and released through co-localized synaptic vesicles, or they can be stored in different groups of vesicles to transmit signals together (Table 1) [12].

Neurotransmitter	Category	Function
Acetylcholine (ACh)		Contraction of smooth muscle cells, slowing of heart rate in cardiac muscle cells, secretion of glandular cells
Norepinephrine (NE)	Catecholamines	Contraction of smooth muscle cells, acceleration of heart rate in cardiac muscle cells
Serotonin	Indolamines	Modulation of autonomic function
Gamma-aminobutyric acid (GABA)	Amino acids	Inhibition of autonomic function
Glutamate	Amino acids	Excitation of autonomic function
Adenosine triphosphate (ATP)	Purines	Modulation of autonomic function
Nitric oxide (NO)	Soluble gases	Modulation of autonomic function

Table 1.

Neurotransmitters of the Autonomic Nervous System.

Some neurotransmitters can be both excitatory and inhibitory depending on the receptor to which they bind, and their functions can vary depending on the specific location and target of the autonomic nervous system.

Research has also shown that neurotransmitters can have multiple functions within the ANS. Acetylcholine, for example, was previously thought to be exclusively responsible for parasympathetic signaling, whereas norepinephrine was thought to be responsible for sympathetic signaling. However, acetylcholine can also be released from sympathetic neurons and act as a modulator of sympathetic activity [6].

ANS has two types of receptors: cholinergic and adrenergic. Acetylcholine activates the cholinergic receptors, while catecholamines such as epinephrine and norepinephrine activate the adrenergic receptors. Cholinergic receptors are divided into two categories: nicotinic receptors and muscarinic receptors. Nicotinic receptors are mainly located in the autonomic ganglia and neuromuscular junction, whereas muscarinic receptors are located in the effector organs of the PNS and some tissues innervated by the SNS. Adrenergic receptors are divided into alpha and beta receptors. Alpha receptors have two subtypes, alpha-1 and alpha-2 receptors. Alpha-1 receptors are located in the smooth muscle of blood vessels and in the iris of the eye, while alpha-2 receptors are located in presynaptic neurons and inhibit the release of norepinephrine. Beta receptors are also of two subtypes, beta-1 and beta-2 receptors. Beta-1 receptors are located in the heart, while beta-2 receptors are found in lung smooth muscle and skeletal muscle. ANS has regulatory systems such as self-inhibition of norepinephrine release via presynaptic alpha-2 receptors, regulation of norepinephrine synthesis, and desensitization and hypersensitization of adrenoceptors. Acetylcholine acts on two classes of receptors: nicotinic receptors, found mainly in ganglia, and muscarinic receptors, which are coupled to G proteins and respond more slowly. Among purine receptors, there are two main types: P1 receptors, which are sensitive to adenosine and blocked by methylxanthines, and P2 receptors, which are sensitive to ATP and can lead to prostaglandin synthesis. Neuropeptide receptors are G protein-coupled receptors that activate adenylyl cyclase or phospholipase C as signal transducers [13, 14, 15].

3.1 Acetylcholine

Acetylcholine is a chemical messenger produced by neurons in various parts of the nervous system. It is released by large pyramidal cells in the motor cortex, various neurons in the basal ganglia, and motor neurons controlling skeletal muscles, among others. Acetylcholine usually has a stimulatory effect on nerve cells, but it can also inhibit certain peripheral parasympathetic nerves, such as those that slow the heart. Choline acetyltransferase (ChAT) is the enzyme responsible for the synthesis of acetylcholine from choline and acetyl coenzyme A in the cytoplasm of nerve cells. After production, acetylcholine is stored in tiny vesicles that have a specific transporter in their membrane. When electrical signals trigger the release of calcium ions, acetylcholine is released into the synaptic cleft, where it can bind to receptors on nearby cells. Acetylcholinesterase is an enzyme that breaks down acetylcholine, limiting its action. The breakdown of acetylcholine produces choline, which is then transported back into neurons to form more acetylcholine. The uptake of choline into the presynaptic terminal is a crucial step in the production of acetylcholine [6].

3.2 Norepinephrine

The neurotransmitter norepinephrine is synthesized by three enzymes and released by neurons in the brainstem and hypothalamus, particularly in the locus ceruleus of the pons. Terminals of these neurons release norepinephrine into the extracellular space by exocytosis triggered by electrical stimulation and a Ca²⁺-dependent process. Norepinephrine is stored in small and large dense nuclear vesicles in the neuronal cytosol alongside chromogranins and dopamine-β-hydroxylase. Its action is rapidly terminated when it interacts with specific receptors by being recycled into neuronal nodes or non-neuronal cells. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) metabolize norepinephrine in intracellular cells. Norepinephrine controls overall activity and mood of the mind by transmitting nerve fibers to different brain areas, resulting in increased alertness. In most of these areas, norepinephrine activates excitatory receptors, although in some regions it triggers inhibitory receptors instead. The post-ganglionic neurons of the SNS secrete NE, which has both excitatory and inhibitory effects on various organs [1, 16].

3.3 ATP

Adenosine triphosphate (ATP), a type of purine nucleotide, was originally identified as the first neurotransmitter in nonadrenergic noncholinergic (NANC) nerves that met the criteria for a neurotransmitter. Further research has shown that purinergic signaling is widespread in both neural and non-neural systems. ATP acts as a neurotransmitter at neuroeffectors, synapses in peripheral autonomic ganglia, and in the brain and spinal cord. It also plays a critical role as a signaling molecule in the enteric nervous system and on sensory nerves affecting both physiological reflexes and nociception. ATP is synthesized in nerve terminals and stored in vesicles. Once released, it binds to post-functional P2X ion channel receptors and is rapidly cleaved by ectonucleotidases into adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine. Adenosine is then transported back into neurons and non-neuronal cells via a high-affinity nucleoside carrier uptake system. It can be converted back to ATP and returned to vesicles or further degraded by adenosine deaminase to inosine, which is inactive and enters the bloodstream. Adenosine acts on prefunctional P1 receptors and inhibits neurotransmitter release. In addition, small amounts of other nucleotides such as ADP, AMP, guanosine triphosphate (GTP), uridine triphosphate (UTP) and diadenosine polyphosphates have been detected in synaptic vesicles, which may also have a neuromodulatory function in the nervous system [3, 17].

3.4 Nitric oxide

NO is a putative neurotransmitter in the ANS that is synthesized in a reaction in which L-arginine is converted to L-citrulline by nitric oxide synthase (NOS). Unlike other neurotransmitters, NO is not stored in vesicles but is synthesized almost instantaneously on demand and diffuses from presynaptic terminals to act on intracellular guanylate cyclase in the post-synaptic neuron, resulting in relaxation. Type I NOS, which is constitutively expressed in autonomic neurons, is stimulated by Ca²⁺ during transmission. NO does not act on extracellular receptors but rather at intracellular sites, and its unstable nature allows it to terminate NO-dependent responses without the need for degradative enzymes or reuptake. In addition, NO can readily bind to the heme group of hemoglobin and inhibits NO-dependent reactions. Nitric oxide is not only found in the autonomic nervous system, but is also produced by nerve terminals in brain regions responsible for long-term behavior and memory. Its unique mechanism of formation in the presynaptic terminal and its action on the post-synaptic neuron distinguish it from other small molecule transmitters. NO is synthesized almost immediately and diffuses out of the presynaptic terminals within seconds rather than being released in vesicular packets. Once in the post-synaptic neuron, it does not significantly alter membrane potential but modifies intracellular metabolic functions to alter neuronal excitability for seconds, minutes, or possibly even longer. Therefore, NO could shed light on previously unexplained behavioral and memory functions [18, 19].

3.5 Other neurotransmitters

The ANS uses several neurotransmitters to regulate various physiological functions. One of these neurotransmitters is 5-hydroxytryptamine (5-HT), which is synthesized from tryptophan via 5-hydroxytryptophan by tryptophan hydroxylase and l-aromatic amino acid decarboxylase. Hydroxytryptamin (HT) While 5-hydroxytryptophan is primarily synthesized in myenteric neurons, it can also act as a spurious neurotransmitter after being taken up and released by sympathetic nerves. Similarly, dopamine, GABA, and glutamate, which are classic neurotransmitters in the central nervous system, also act as autonomic neurotransmitters. GABA is the major inhibitory neurotransmitter in the adult central nervous system and is secreted by nerve terminals in the spinal cord, cerebellum, basal ganglia, and many areas of the cortex. The role of GABA in enteric neurotransmission has been identified, where it acts through excitatory GABAA and prefunctional inhibitory GABAB receptors. Dopamine is secreted by neurons from the substantia nigra, terminating mainly in the striatal region of the basal ganglia. Its action is primarily inhibitory. Glutamate is secreted from presynaptic terminals in many sensory pathways entering the central nervous system and in many areas of the cerebral cortex and is known to cause excitation. Serotonin, secreted by nuclei in the median raphe of the brainstem, acts as an inhibitor of pain pathways in the spinal cord and contributes to mood control and sleep initiation in higher regions of the nervous system [1, 20].

3.5.1 Hydrogen sulfide (H2S)

H2S is a colorless, flammable gas that has long been known as a toxic environmental pollutant. However, recent studies have shown that H2S is also an endogenously produced gasotransmitter that plays a crucial role in various physiological processes in the body. H2S is produced by the enzyme cystathionine beta synthase as part of the transsulfuration pathway that converts homocysteine to cysteine. Another enzyme, cystathionine gamma lyase, can also produce H2S from cysteine. The third H2S-producing enzyme, 3-mercaptopyruvate sulfurtransferase, produces H2S from 3-mercaptopyruvate. H2S can also be produced by the gut microbiota, which metabolizes sulfur-containing amino acids. Once produced, H2S acts as a signaling molecule that regulates various physiological processes, including blood pressure, inflammation, and cell signaling. H2S has also been shown to have anti-inflammatory, antioxidant, and cytoprotective effects. One of the most important physiological processes regulated by H2S is vasodilation, which contributes to the regulation of blood pressure. H2S induces vasodilation by activating ATP-sensitive potassium channels in vascular smooth muscle cells. This leads to hyperpolarization of the cell membrane, resulting in smooth muscle cell relaxation and subsequent vasodilation. H2S also has an anti-inflammatory effect. It can inhibit the production of pro-inflammatory cytokines such as interleukin-1 beta (IL-1B), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). This anti-inflammatory effect is thought to be mediated by inhibiting the activation of nuclear factor kappa B (NF-kB), which is an important regulator of the inflammatory response. In addition, H2S has been shown to have a cytoprotective effect. It can protect cells from oxidative stress-induced damage and apoptosis. H2S can also increase the activity of antioxidant enzymes such as superoxide dismutase and catalase, which also contributes to its cytoprotective effect. Overall, H2S is a gasotransmitter that plays a crucial role in regulating various physiological processes in the body. Its vasodilatory, anti-inflammatory, and cytoprotective effects make it a promising therapeutic target for the treatment of various diseases such as hypertension, inflammation, and oxidative stress-related disorders [21, 22].

3.5.2 Neuropeptide Y

NPY is a 36 amino acid neuropeptide widely distributed in the central and peripheral nervous system. It belongs to the peptide family, which also includes peptide YY (PYY) and pancreatic polypeptide (PP). NPY acts as a neurotransmitter in the brain, where it is involved in a number of physiological functions, including appetite regulation, stress response, anxiety, and mood regulation. NPY is also found in the peripheral nervous system, where it regulates cardiovascular function, gastrointestinal motility, and immune function. In humans, the NPY gene is located on chromosome 7, and the peptide is synthesized in the cell bodies of neurons in the brain and peripheral nervous system. NPY is released by nerve terminals in response to a variety of stimuli, including stress, fasting, and exercise. NPY exerts its effects by binding to a family of G protein-coupled receptors called Y receptors. There are five known Y receptors (Y1, Y2, Y4, Y5, and Y6), each of which has a different distribution pattern in the brain and peripheral tissues. The Y1 receptor is the most abundant subtype in the brain and is involved in the regulation of feeding behavior, anxiety, and pain perception. The Y2 receptor is also found in the brain and is involved in modulating the release of neurotransmitters. The Y4 and Y5 receptors are mainly found in the periphery, where they regulate food intake, adiposity, and glucose homeostasis. The Y6 receptor is expressed in the brain, but its function is not well understood. NPY is associated with a number of human diseases, including obesity, diabetes, anxiety, and cardiovascular disease. In obesity, elevated levels of NPY have been observed, leading to increased food intake and weight gain. In diabetes, NPY has been shown to play a role in regulating glucose homeostasis, and drugs targeting the Y2 receptor have been suggested as potential therapies [23, 24, 25].

3.5.3 Orexin

Another recently discovered ANS neurotransmitter is orexin, also known as hypocretin. It is a neuropeptide produced mainly in a small group of neurons in the hypothalamus of the brain. This neuropeptide plays an important role in regulating various physiological processes, including sleep, wakefulness, feeding behavior, energy homeostasis, and reward systems.

Orexin was first discovered in 1998, and since then, extensive research has been conducted to understand its functions in the brain. One of the most important roles of orexin is its involvement in sleep regulation. Orexin neurons are active during periods of wakefulness and promote wakefulness by stimulating the release of other neurotransmitters such as dopamine, norepinephrine, and histamine. These neurotransmitters ensure that the brain remains in a state of arousal and alertness. In addition, orexin has been found to play a critical role in regulating feeding behavior and energy homeostasis. Orexin promotes feeding behavior by increasing appetite and enhancing the rewarding properties of food. This neuropeptide also regulates energy expenditure by increasing thermogenesis, or heat production, in brown adipose tissue. Studies also suggest that orexin may be involved in the development of addiction and drug-seeking behavior. This neuropeptide has been found to enhance the rewarding effects of drugs such as cocaine and amphetamines by stimulating the release of dopamine in the brain’s reward centers. In addition, recent studies have shown that orexin may play a role in regulating emotional behaviors such as anxiety and depression. Orexin signaling has been found to be disrupted in people with anxiety and depressive disorders, and modulation of orexin signaling has been suggested as a potential therapeutic target for these disorders [26, 27].

3.5.4 PACAP

Pituitary adenylate-cyclase-activating polypeptide (PACAP) is a neuropeptide that acts as a neurotransmitter or neuromodulator in the central and peripheral nervous systems. It was first discovered in the hypothalamus, where it has been shown to stimulate the release of adrenocorticotropic hormone from the pituitary gland. Since then, PACAP has been found to have a variety of functions in the nervous system, including regulating the release of neurotransmitters, modulating synaptic plasticity, and maintaining neuronal survival. One of the most important functions of PACAP in the nervous system is the regulation of neurotransmitter release. PACAP has been shown to stimulate the release of several neurotransmitters, including acetylcholine, norepinephrine, and dopamine, from both central and peripheral neurons. This suggests that PACAP may play an important role in regulating autonomic function as well as modulating higher brain functions such as learning and memory. PACAP also plays a critical role in synaptic plasticity, the process by which the strength of synapses between neurons is altered in response to changes in neuronal activity. In particular, PACAP has been shown to enhance long-term potentiation, a form of synaptic plasticity thought to underlie learning and memory. This suggests that PACAP could be an important target for the development of drugs to improve cognitive function. Another important function of PACAP in the nervous system is to maintain neuron survival. PACAP has been shown to protect neurons from a range of damage, including oxidative stress, ischemia, and excitotoxicity [28, 29]. This suggests that PACAP may have therapeutic potential for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

3.5.5 Galanin

Recent research has identified the neuropeptide galanin as another important ANS neurotransmitter. Galanin is a neuropeptide widely distributed in the central and peripheral nervous system. It was first discovered in the pig intestine in 1983, but later studies showed that it is also expressed in the brain and various other tissues. Galanin is synthesized as a precursor protein and then cleaved into smaller peptides that are released by nerve terminals as neurotransmitters or neuromodulators. Galanin acts on three different G protein-coupled receptors, namely GAL1, GAL2, and GAL3. These receptors are widely distributed in the brain and peripheral tissues, suggesting that galanin has multiple biological effects. In the nervous system, galanin is involved in the regulation of a variety of functions, including feeding, pain perception, memory, and anxiety. One of the most important functions of galanin in the nervous system is its involvement in pain modulation. Galanin has been shown to inhibit the release of substance P, a neuropeptide involved in the transmission of pain signals. Galanin also regulates the activity of nociceptors, the primary sensory neurons that respond to painful stimuli. These effects of galanin suggest that it is a potential therapeutic agent for the treatment of chronic pain. In addition to its role in pain modulation, galanin is also involved in the regulation of feeding behavior. Studies have shown that galanin stimulates feeding behavior in animals, and blocking its activity can lead to decreased food intake and weight loss. The GAL1 receptor has been identified as the main mediator of galanin’s effects on feeding behavior, making it a potential target for the treatment of obesity. Galanin has also been associated with the regulation of memory and anxiety. Studies have shown that galanin levels are altered in the brains of animals exposed to stress and that administration of galanin can attenuate the behavioral and neurochemical effects of stress. These results suggest that galanin may play a protective role against the negative effects of stress on the brain and that it has potential for treating anxiety [30, 31, 32].

3.5.6 Taurine

Taurine, an amino acid with neuroprotective properties, plays a crucial role in regulating various cellular processes in the central nervous system. Taurine acts as a neuromodulator within the ANS, affecting neuronal excitability and autonomic functions. It has been shown to have a significant impact on neural stem and progenitor cells through modulation of gene expression. Taurine exerts its protective effects by influencing inflammatory processes in the central nervous system, inhibiting apoptosis, acting as an antioxidant, and controlling cell volume and water content in neurons. One of the most important mechanisms by which taurine provides neuroprotection is the suppression of apoptosis or programmed cell death. Taurine acts on both ionotropic taurine receptors and metabotropic taurine receptors to inhibit apoptosis triggered by stress in the endoplasmic reticulum (ER). By attenuating apoptosis triggered by ER, taurine helps to ensure neuron survival and prevent neuronal damage. In addition, taurine has antioxidant properties that effectively scavenge free radicals and reduce oxidative stress in the central nervous system. This antioxidant activity helps protect neurons from oxidative damage and contributes to the overall neuroprotective effects of taurine. The neuroprotective properties of taurine have made it a promising candidate for the prophylaxis and treatment of neurodegenerative diseases [33, 34, 35, 36, 37].

4. Conclusion

The ANS plays a critical role in maintaining homeostasis and regulating physiological functions throughout the body. Neurotransmitters serve as important mediators in the transmission of signals within the ANS and enable precise communication between neurons and their target tissues or organs. In this comprehensive exploration of the neurotransmitters of the autonomic nervous system, we have gained valuable insights into their intricate mechanisms and physiological effects. Recent advances in our understanding of the ANS have been driven by the identification of new neurotransmitters and their functions. These findings have led to a more comprehensive understanding of the complex mechanisms that regulate various physiological processes. The discovery of new ANS neurotransmitters has opened new possibilities for targeted treatments of autonomic disorders. Precise targeting of these neurotransmitters could lead to more effective therapies with fewer side effects than current treatments. In addition, the discovery of new neurotransmitters has shed light on the intricate signal transduction pathways underlying ANS regulation. By studying these pathways, researchers can gain a deeper understanding of how different physiological systems interact to maintain homeostasis in the body. As research in this area continues to advance, we can expect to gain further insight into the functions of ANS neurotransmitters and their role in regulating physiological processes. These discoveries promise new treatments and therapies for autonomic disorders, as well as a more comprehensive understanding of the complexity of the autonomic nervous system.