Peripheral nervous system transmitters

Peripheral nervous system Nerve tissues lying outside the brain and spinal cord, functions include the transmittal of sensory information such as touch, heat, cold, and pain, and the motor impulses for limb movement. 

Acetylcholine (Ach) is an ester of acetic acid and choline with the chemical formula CH3COOCH2CH2N+ (CH3)3. ACh functions as a chemical transmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in a wide range of organisms, humans included. Neurotransmitter involved in behavioral state control, postural tone, cognition and memory, and autonomous parasympathetic (and preganglionic sympathetic) nervous system. 

NPY is primarily (but not exclusively) synthesised and released by neurons, which in the peripheral nervous system are predominantly sympathetic neurons [1]. In most cases, NPY acts as a co-transmitter that is preferentially released upon high frequency nerve stimulation. NPY can be metabolised by the enzyme dipeptidylpeptidase IV (also known as CD26) to generate the biologically active fragment NPY3 36. 

It is easy to speculate that in an active neuron with a rapid firing pattern, the continued release of a peptide may eventually lead to depletion of the peptide occurring. This has been shown in the peripheral nervous system. If this also happens in the CNS it would provide a mechanism whereby the release and resultant receptor effects of a transmitter no longer match the firing pattern and demands of the neuron and so could contribute to long-term adaptations of neurons by a reduction in the time over which a peptide is effective. 

In addition to the physiological process of autoinhibition, another mechanism of presynaptic inhibition has been identified in the peripheral nervous system, although its precise relevance to the brain is unclear. In the dorsal horn of the spinal cord, for example, the axon terminal of a local neuron makes axo-axonal contact with a primary afferent excitatory input, which leads to a reduction in the neurotransmitter released. This is due to the local neuron partly depolarizing the nerve terminal, so that when the axon potential arrives, the change induced is diminished, thereby leading to a smaller quantity of transmitter being released. In the brain, it is possible that GABA can cause presynaptic inhibition in this way. 

The rate-limiting step in the synthesis of the catecholamines from tyrosine is tyrosine hydroxylase, so that any drug or substance which can reduce the activity of this enzyme, for example by reducing the concentration of the tetrahydropteridine cofactor, will reduce the rate of synthesis of the catecholamines. Under normal conditions tyrosine hydroxylase is maximally active, which implies that the rate of synthesis of the catecholamines is not in any way dependent on the dietary precursor tyrosine. Catecholamine synthesis may be reduced by end product inhibition. This is a process whereby catecholamine present in the synaptic cleft, for example as a result of excessive nerve stimulation, will reduce the affinity of the pteridine cofactor for tyrosine hydroxylase and thereby reduce synthesis of the transmitter. The experimental drug alpha-methyl-para-tyrosine inhibits the rate-limiting step by acting as a false substrate for the enzyme, the net result being a reduction in the catecholamine concentrations in both the central and peripheral nervous systems. 

The effects on sleep result from the psychostimulant and sympathomimetic actions of these drugs. They enhance noradrenergic, dopaminergic and serotonergic transmission in the central and peripheral nervous system mainly by increasing transmitter release and also inhibitory uptake. 

The discovery that ACh was a transmitter in the peripheral nervous system formed the basis for the theory of neurotransmission. ACh is also a neurotransmitter in the mammalian brain however, only a few cholinergic tracts have been clearly delineated. ACh is an excitatory neurotransmitter in the mammalian CNS. There is good evidence that ACh (among other neurotransmitters) is decreased in certain cognitive disorders, such as Alzheimer s disease. 

Cannabinoid and endocannabinoid-induced synaptic depression is observed in both the peripheral nervous system and the CNS. Indeed, A9-THC inhibition of transmitter release was first demonstrated in mouse vas deferens (Graham et al. 1974), and further evidence for presynaptic inhibition has been obtained using this preparation (Ishac et al. 1996 Pertwee and Fernando 1996) and in the myenteric plexus (Coutts and Pertwee 1997 Kulkami-Narla and Brown 2000). In addition, anandamide was first characterized as an EC based on its actions in the mouse vas deferens (Devane et al. 1992). Subsequently, CB1 receptor-mediated inhibition of release of several neurotransmitters has been documented in various regions of the PNS (see Szabo and Schlicker 2005 for review). Cannabinoids also inhibit neural effects on contraction in the ileum (Croci et al. 1998 Lopez-Redondo et al. 1997), although it is not clear that this is effect involves direct inhibition of neurotransmitter release (Croci et al. 1998). The CB1 receptor has been localized to enteric neurons, and thus the effect on ileum certainly involves actions on these presynaptic neurons. In addition, anandamide produces ileal relaxation via a non-CBl, non-CB2-mediated mechanism (Mang et al. 2001). 

Mechanism of action As with cocaine, the effects of amphetamine on the CNS and peripheral nervous system are indirect that is, they depend upon an elevation of the level of catecholamine transmitters in synaptic spaces. Amphetamine, however, achieves this effect by releasing intracellular stores of catecholamines (Figure 10.7). Since amphetamine also blocks monoamine oxidase (MAO), high levels of catecholamines are readily released into synaptic spaces. Despite different mechanisms of action, the behavioral effects of amphetamine are similar to those of cocaine. 

Norepinephrine (NE), a catecholamine, was first identified as a neurotransmitter in 1946. In the peripheral nervous system, it is found as a neuro transmitter in the sympathetic postganglionic synapse. NE is synthesized by the enzyme dopamine-p-hydroxylase (DbH) from the precursor dopamine (which is derived from tyrosine via DOPA). The rate-limiting step is the production of DOPA by tyrosine hydroxylase, which can be activated through phosphorylation. NE is removed from the synapse by two mechanisms (1) catechol-O-methyl-transferase (COMT), which degrades intrasynaptic NE, and (2) the norepinephrine transporter (NET), the primary way of removing NE from the synapse. Once internalized, NE can be degraded by the intracellular enzyme monoamine oxidase (MAO). 

Acetylcholine (ACh, 51-84-3) is a molecular ion which functions as a neurohumoral transmitter in the peripheral nervous system. It is released at the end of one cell, diffuses across the synapse, induces permeability changes in the next cell, and is then rapidly removed from the synaptic region by a hydrolytic reaction catalvzed by the enzyme acetylcholinesterase (AChE,... 

FIGURE 5.2 (See color insert following page 46.) Presynaptic and postsynaptic regions of the acetylcholine neuron, emphasizing the synthesis and degradation of acetylcholine and the cholinergic receptor suhtypes (Panel [A]) summary of the peripheral nervous system that utilizes acetylcholine as the transmitter (Panel [ B]). 

Abstract The CBi cannabinoid receptor is widely distributed in the central and peripheral nervous system. Within the neuron, the CBi receptor is often localised in axon terminals, and its activation leads to inhibition of transmitter release. The consequence is inhibition of neurotransmission via a presynaptic mechanism. Inhibition of glutamatergic, GABAergic, glycinergic, cholinergic, noradrenergic and serotonergic neurotransmission has been observed in many regions... 

The pharmacology of insect central nervous system transmitter receptors and their associated modulatory sites and ion channels is less thoroughly known than that of the peripheral neuromuscular systems. This is in part due to the relative inaccessibility of the central... 

In the peripheral nervous system, noradrenaline is accepted as the alternative transmitter substance to acetylcholine, mediating the transmission of impulses from most of the postganglionic sympathetic fibres to their effector organs. The evidence that noradrenaline also has a transmitter function in the central nervous system is less clear. 

No P2 effects. Thus it cannot be used as a bronchodilator. Relatively weak i insulin release (a2), lipolysis (Pl). Endogenous transmitter of the peripheral nervous system. Used only when intense vasoconstriction is necessary (septic shock). 

The first molecules identified as transmitters of information within both the peripheral nervous system (PNS) and brain (CNS) were acetylcholine (ACh), norepinephrine (NE), and 5-HT. ACh is the neurotransmitter in the autonomic nervous system Profound biological effects can result from even shght changes of molecular configuration. 

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