The action of nerves

The structure of a typical nerve is shown in Fig. A2.1. The nucleus of the cell is found in the large cell body situated at one end of the nerve cell. Small arms (dendrites) radiate from the cell body and receive messages from other nerves. These messages either stimulate or destimulate the nerve. The cell body collects the sum total of these messages. 

Assuming that the overall stimulation is great enough, an electrical signal is fired down the length of the nerve (the axon). This axon is padded with sheaths of lipid (myelin sheaths) which act to insulate the signal as it passes down the axon. 

The axon leads to a knob-shaped swelling (synaptic button) if the nerve is communicating with another nerve. Alternatively, if the nerve is communicating with a muscle cell, the axon leads to what is known as a neuromuscular endplate, where the nerve cell has spread itself like an amoeba over an area of the muscle cell. 

Within the synaptic button or neuromuscular endplate there are small globules 

To date, we have talked about nerves firing and the generation of electrical signals without really considering the mechanism of these processes. The secret behind nerve transmission lies in the movement of ions across cell membranes, but there is an important difference in what happens in the cell body of a nerve compared to the axon. We shall consider what happens in the cell body first. 

---

One form of biological poisoning mirrors the effect of lead on a catalytic converter. The activity of an enzyme is destroyed if an alien substrate attaches too strongly to the enzyme s active site, because then the site is blocked and made unavailable to the true substrate (Fig. 13.42). As a result, the chain of biochemical reactions in the cell stops, and the cell dies. The action of nerve gases is believed to stem from their ability to block the enzyme-controlled reactions that allow impulses to travel through nerves. Arsenic, that favorite of fictional poisoners, acts in a similar way. After ingestion as As(V) in the form of arsenate ions (As043 ), it is reduced to As(III), which binds to enzymes and inhibits their action. 

Treatment—Since C. botulinum toxin blocks the actions of nerves that activate muscles necessary for breathing, an antitoxin can be injected up to about 24 hours (based on monkey studies) after exposure to a lethal toxin dose and still prevent death. The two types of available antitoxins prepared from horse sera are trivalent (includes types A, B, E) and heptavalent (types A, B, C, D, E, F, and G) preparations. It should be noted that patients face a theoretical risk of developing serum sickness from such antitoxins. 

They did not report the minimum lethal dose or any other quantitative measure of toxicity, but nobody reading their paper would have missed the fact that the compounds are violently poisonous. During World War II, research on the fluorophosphonates was carried on for military purposes, and Adrian and his coworkers in Britain noted the similarity between the physiological action of the fluorophosphonates and that of reversible inhibitors of choline esterase (Adrian et al., 1947). This led to a number of scientific investigations of the action of nerve gases on various esterases. 

Mutoh, T., Tokuda, A., Inokuchi, J., and Kuriyama, M. (1998). Glucosylceramide synthase inhibitor inhibits the action of nerve growth factor in PC 12 cells. J. Biol. Chem. 273, 26001—26007. 

In summary, acetylcholine produces an erection by working along with other co-neurotransmitters, including cGMP and cAMP, as described earlier. Thus an erection is initiated by the action of nerves, maintained by arterial blood filling of the corpora, and sustained by occlusion of venous outflow from the corpora. 

An inhibitory effect is exerted by oximes on the luminol/hydrogen peroxide reaction [43]. It has been claimed that it mimics certain processes connected with the action of nerve gases on cholinesterase (see next Section) although the connection is tenuous. Oximes are in fact capable of removing the inhibition exerted on cholinesterase by nerve gases [44] and it has been suggested that chemiluminescence can be used to monitor this. 

Histamine AND histamine antagonists). It is formed from histidine by the enzyme L-histidine decarboxylase. In the periphery, histamine is stored ia mast cells, basophils, cells of the gastric mucosa, and epidermal cells. In the CNS, histamine is released from nerve cells and acts as a neurotransmitter. The actions of histamine ate terrninated by methylation and subsequent oxidation via the enzymes histamine-/V-methyltransferase and monoamine oxidase. 

Dmgs that mimic or inhibit the actions of neurotransmitters released from parasympathetic or sympathetic nerves innervating the heart may also be used to treat supraventricular bradyarrhythmias, heart block, and supraventricular tachyarrhythmias. Those used in the treatment of arrhythmias may be found in Table 1. 

The same author found Z-hyoscine sixteen to eighteen times as active as the d-isomeride in antagonising the action of pilocarpine on the termination of nerves in the salivary glands, -while both isomerides are equally active on nerve ends in striated and unstriated muscle and on the central nervous system. 

In a monograph on ephedrine Gaddum has reviewed the differences in the action of adrenaline and ephedrine and has suggested that the latter has the same relation to adrenaline as physostigmine has to acetylcholine, that is, ephedrine inhibits the action of an enzyme system, which normally destroys adrenaline, or the substance closely resembling it, produced by adrenergic nerves. 

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

The adrenergic system is an essential regulator that increases cardiovascular and metabolic capacity during situations ofstress, exercise, and disease. Nerve cells in the central and peripheral nervous system synthesize and secrete the neurotransmitters noradrenaline and adrenaline. In the peripheral nervous system, noradrenaline and adrenaline are released from two different sites noradrenaline is the principal neurotransmitter of sympathetic neurons that innervate many organs and tissues. In contrast, adrenaline, and to a lesser degree noradrenaline, is produced and secreted from the adrenal gland into the circulation (Fig. 1). Thus, the actions of noradrenaline are mostly restricted to the sites of release from sympathetic nerves, whereas adrenaline acts as a hormone to stimulate many different cells via the blood stream. 

Excitability refers to the capacity of nerves and other tissues (e.g. cardiac), as well as individual cells, to generate and sometimes propagate action potentials, signals that serve to control intracellular processes, such as muscle contraction or hormone secretion, and to allow for long- and short-distance communication within the organism. Examples of excitable cells and tissues include neurons, muscle and endocrine tissues. Examples of nonexcitable cells and tissues include blood cells, most epithelial and connective tissues. 

Histamine is synthesized from the amino acid histidine via the action of the specific enzyme histidine decarboxylase and can be metabolized by histamine-TV-methyl transferase or diamine oxidase. Interesting, in its role as a neurotransmitter the actions of histamine are terminated by metabolism rather than re-uptake into the pre-synaptic nerve terminals. 

Purinergic System. Figure 2 Schematic of sympathetic cotransmission. ATP and NA released from small granular vesicles (SGV) act on P2X and a-i receptors on smooth muscle, respectively. ATP acting on inotropic P2X receptors evokes excitatory junction potentials (EJPs), increase in intracellular calcium ([Ca2+]j) and fast contraction while occupation of metabotropic ar-adrenoceptors leads to production of inositol triphosphate (IP3), increase in [Ca2+]j and slow contraction. Neuropeptide Y (NPY) stored in large granular vesicles (LGV) acts after release both as a prejunctional inhibitory modulator of release of ATP and NA and as a postjunctional modulatory potentiator of the actions of ATP and NA. Soluble nucleotidases are released from nerve varicosities, and are also present as ectonucleotidases. (Reproduced from Burnstock G (2007) Neurotransmission, neuromodulation cotransmission. In Squire LR (ed) New encyclopaedia of neuroscience. Elsevier, The Netherlands (In Press), with permission from Elsevier). 

---