Purinergic regulation of acetylcholine release

• Type: Another Publication in an International Scientific Journal
• Date: 1996

Authors

Ribeiro, JA (Author) Other; Cunha, RA (Author) Other; Paulo Correia de Sá (Author) Other; Sebastiao, AM (Author) Other

Journal

Title: Progress in Brain Research

Vol. 73

Pages: 231-241

ISSN: 0079-6123

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 49 Citations

Scopus - 56 Citations

Other information

Authenticus ID: P-001-F27

DOI: 10.1016/s0079-6123(08)62107-x

Abstract (EN): At the neuromuscular junction and possibly also at the synaptic level in the brain, the main sequence of events that involves purines in modulation of ACh release includes the following observations: (1) storage of ATP and its release either together with, or independently of acetylcholine. ATP is also released from the postjunctional component. Adenosine as such is released either from the motor nerve terminals or from the post-junctional component. (2) There is extracellular hydrolysis of ATP to adenosine, which is the active substance to modulate transmitter release. The key enzyme in the conversion of AMP into adenosine is the ecto 5'-nucleotidase. When ecto-5'-nucleotidase is not available (e.g. in cholinergic nerve terminals of the cerebral cortex) ATP as such exerts the neuromodulatory role normally fulfilled by adenosine. (3) Both the inhibition and the excitation induced by adenosine on ACh release in the rat is inactivated through uptake and deamination. (4) Adenosine-induced inhibition of ACh release is mediated via A1 receptors and the excitation via A(2a) receptors. The A(2a) receptors are positively coupled to the adenylate cyclase/cyclic AMP system, whereas the presynaptic A1 receptors (a) may be negatively linked to adenylate cyclase and (b) to phospholipase C, and, upon stimulation, (c) increase potassium conductance and (d) decrease calcium conductance. (5) Activation of A(2a) receptors is essential for substances that facilitate ACh release (e.g. CGRP, forskolin) to exert their effects, as well as for induction of nicotinic autofacilitatory receptor desensitization. (6) There are interactions between A1 and A(2a) receptors. Thus, the net adenosine neuromodulatory response is the resultant, at each moment, of the relative degree of activation of each one of these receptors. This relative activation depends upon the intensity (frequency, pulse duration) of stimulation of the motor nerve terminals. (7) Adenosine released as such seems to preferentially activate A1 receptors, whereas the adenosine formed from metabolism of adenine nucleotides prefers to activate the A(2a) receptors. In conclusion, to find out precisely what occurs with ACh in transmitting its message at the synaptic level, one has to consider the subtle ways used by purines to modulate the ACh response. It therefore appears of interest that pharmacological and therapeutic strategies use this knowledge to approach cholinergic transmission deficiencies based upon reduction of ACh release.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11