Transmitter substance

Synaptic transmission is the transfer of biological information across synapses. Drugs that influence synaptic transmission play an eminent role in therapy, for two reasons. First, the nervous system controls all tissues. Second, with few exceptions synaptic transmission is chemical, operating by means of transmitter substances, and synapses therefore provide a large number of drug targets, such as the enzymes that synthesize the transmitter. However, the importance of... 

There are numerous transmitter substances. They include the amino acids glutamate, GABA and glycine acetylcholine the monoamines dopamine, noradrenaline and serotonin the neuropeptides ATP and NO. Many neurones use not a single transmitter but two or even more, a phenomenon called cotransmission. Chemical synaptic transmission hence is diversified. The basic steps, however, are similar across all neurones, irrespective of their transmitter, with the exception of NO transmitter production and vesicular storage transmitter release postsynaptic receptor activation and transmitter inactivation. Figure 1 shows an overview. Nitrergic transmission, i.e. transmission by NO, differs from transmission by other transmitters and is not covered in this essay. 

Bumstock, G, Campbell, G, Satchell, D and Smythe, A (1970) Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. Brit. J. Pharmacol. 40 668-688. 

It is a measure of the changed outlook among neurophysiologists that it has been thought appropriate to include. ..[here]. .. a discussion on the nature of synaptic transmitter substances other than acetylcholine. A few years ago, the whole hypothesis of the chemical mediation of impulse transmission across central synapses was meeting so much opposition that the energies of those who supported it had to be concentrated on the claims of acetylcholine. ... 

The natural sympathetic transmitter substance (i.e. that released at terminals following sympathetic nerve stimulation) is noradrenaline figure 2. When administered... 

The side effects of tricyclic antidepressants are largely attributable to the ability of these compounds to bind to and block receptors for endogenous transmitter substances. These effects develop acutely. Antagonism at muscarinic cholinoceptors leads to atropine-like effects such as tachycardia, inhibition of exocrine glands, constipation, impaired micturition, and blurred vision. 

The nervous system has several properties in common with the endocrine system, which is the other major system for control of body function. These include high-level integration in the brain, the ability to influence processes in distant regions of the body, and extensive use of negative feedback. Both systems use chemicals for the transmission of information. In the nervous system, chemical transmission occurs between nerve cells and between nerve cells and their effector cells. Chemical transmission takes place through the release of small amounts of transmitter substances from the nerve terminals into the synaptic cleft. The transmitter crosses the cleft by diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule. In a few cases, retrograde transmission may occur from the postsynaptic cell to the presynaptic neuron terminal. 

Schematic diagram comparing some anatomic and neurotransmitter features of autonomic and somatic motor nerves. Only the primary transmitter substances are shown. Parasympathetic ganglia are not shown because most are in or near the wall of the organ innervated. Cholinergic nerves are shown in blue noradrenergic in red and dopaminergic in green. Note that some sympathetic postganglionic fibers release acetylcholine or dopamine rather than norepinephrine. The adrenal medulla, a modified sympathetic ganglion, receives sympathetic preganglionic fibers and releases epinephrine and norepinephrine into the blood. ACh, acetylcholine D, dopamine Epi, epinephrine M, muscarinic receptors N, nicotinic receptors NE, norepinephrine.

Table 6-1 Some of the Transmitter Substances Found in Autonomic Nervous System (ANS), Enteric Nervous System (ENS), and Nonadrenergic, Noncholinergic Neurons.1...

It has been known for many years that autonomic effector tissues (eg, gut, airways, bladder) contain nerve fibers that do not show the histochemical characteristics of either cholinergic or adrenergic fibers. Both motor and sensory NANC fibers are present. Although peptides are the most common transmitter substances found in these nerve endings, other substances, eg, nitric oxide synthase and purines, are also present in many nerve terminals (Table 6-1). Capsaicin, a neurotoxin derived from chili peppers, can cause the release of transmitter (especially substance P) from such neurons and, if given in high doses, destruction of the neuron. 

In most instances the arrival of a nerve signal at the presynaptic end of a neuron causes the release of a transmitter substance (neurohormone). Tire transmitter passes across the 10-50 nm (typically 20 nm) synaptic cleft between the two cells and induces a change in the electrical potential of the postsynaptic membrane of the next neuron (Fig. 30-10).149 401 Excitatory transmitters usually cause depolarization of the membrane. By this we mean that the membrane potential, which in a resting neuron is -50 to -70 mv (Chapter 8), falls to nearly zero often as a consequence of an increased permeability to Na+ and a resultant inflow of sodium ions. The resulting postsynaptic... 

We may now assemble the foregoing information into a molecular description of a few biological processes in which the interaction between water and metal ions plays an important role. First some problems related to signal transfer in nerve cells are discussed. This is followed by some comments on the mechanism operating at nerve synapses in which, in addition to the sodium and potassium ions, a specific transmitter substance and calcium ions take part. 

The principle of negative feedback control is also found at the presynaptic level of autonomic function. Important presynaptic feedback inhibitory control mechanisms have been shown to exist at most nerve endings. A well-documented mechanism involves an 2 receptor located on noradrenergic nerve terminals. This receptor is activated by norepinephrine and similar molecules activation diminishes further release of norepinephrine from these nerve endings (Table 6-4). Conversely, a presynaptic Breceptor appears to facilitate the release of norepinephrine. Presynaptic receptors that respond to the transmitter substances released by the nerve ending are called autoreceptors. Autoreceptors are usually inhibitory, but many cholinergic fibers, especially somatic motor fibers, have excitatory nicotinic autoreceptors. 

Katz B. (1969) The Release of Neural Transmitter Substances. Charles Thomas, Springfield, IL. 

Bioelectric Organization of Nervous Tissue. The membrane potential of 70 mV is developed across the lipid bilayer of the cell membrane. This layer is approximately 40 8 thick, so that the transmembrane electric gradient is of the order of 105 V/cm. This extraordinary dielectric strength is not easily replicated in artificial materials. It is noteworthy that the resting membrane potential maintains this dielectric bilayer within a factor of two of electrical breakdown (19). Release of neural transmitter substances from synaptic terminals on the nerve cell surface transiently shifts the membrane potential at the site of release by a few millivolts. In terms of an altered transmembrane gradient, this shift is of the order of 1.0 kV/cm. 

Katz, B. The release of neural transmitter substances. Thomas, Springfield, Illinois, 1969. 

Evidence is lacking for the presence of the amino acids, y-aminobutyric acid (GABA), glutamic acid, aspartic acid and glycine, which are believed to play a role as transmitter substances in vertebrates and other invertebrates. 

---