Comparative studies of purinergic nerves

Abstract

Purinergic nerves supply the gastrointestinal tract of vertebrates, including fish, amphibians, reptiles and birds, as well as mammals. Their cell bodies are located in Auerbach's plexus and their axons extend in an anal direction before innervating mainly the circular muscle coat. In the stomach they are controlled by preganglionic cholinergic fibres of parasympathetic origin. They are involved in "receptive relaxation" of the stomach, "descending inhibition" in peristalsis and reflex relaxation of oesophageal and internal anal sphincters. The terminal varicosities of purinergic nerves are characterised by a predominance of "large opaque vesicles," which can be distinguished from the "large granular vesicles" found in small numbers in both adrenergic and cholinergic nerves. Stimulation of purinergic nerves with single pulses produces hyperpolarisations of up to 25 mV (inhibitory junction potentials) in smooth muscle cells. These potentials are unaffected by atropine, adrenergic neuron blocking agents or sympathetic denervation, but are abolished by tetrodotoxin. The "rebound contraction" which characteristically follows cessation of purinergic nerve stimulation is probably due to prostaglandin. Evidence that ATP is the transmitter released from purinergic nerves includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (4) the presence of Mg-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) drugs (including quinidine, some 2-substituted imidazolines, 2-2'pyridylisatogen and dipyridamole) which produce similar blocking or potentiating effects on the response to exogenously applied ATP and nerve stimulation. Speculations are made about the evolution and development of the nervous system, including the possibility that purinergic nerves are a primitive nerve type.

Review lecture. Neurotransmitters and trophic factors in the autonomic nervous system.

“…Two essentially opposing views have been put forward for the mechanisms by which new neurotransmitter systems evolve. One view is that neurones have a common phylohistogenetic origin and that they differentiate into various chemical types in the course of evolution due to functional specialization (Burnstock, 1969(Burnstock, , 1975cLentz, 1968). An alternative view is that there were multiple origins of nerve cells, which meant wide diversity of neurotransmitters early in evolution and eventual…”

Adenosine triphosphate stimulates phosphoinositide metabolism, mobilizes intracellular calcium, and inhibits terminal differentiation of human epidermal keratinocytes.

“…Extracellular ATP at low micromolar concentrations influences many biological processes (1) including platelet aggregation (2), vascular tone (3,4), neurotransmission (5,6) and mus-cle contraction (7). Plasma concentrations of ATP can achieve the micromolar range under certain conditions such as secretion from platelets (8,9), purinergic nerves (10), and adrenal medulla (1 1).…”

Comparative Pharmacological and Histochemical Evidence for Purinergic Inhibitory Innervation of the Portal Vein of the Rabbit, but Not Guinea‐pig

“…The widespread occurrence of non-adrenergic, noncholinergic nerves in the autonomic nervous system of vertebrates is well recognised (Burnstock, 1969;1975a;Campbell, 1970). Evidence has been presented that a purine nucleotide, probably adenosine 5'-triphosphate (ATP) is the neurotransmitter in some of these nerves (Burnstock, Campbell, Satchell & Smythe, 1970;Burnstock, 1972;1975b) and they have therefore been termed 'purinergic' (Burnstock, 1971).…”