ATP modulates the efferent function of capsaicin-sensitive neurones in guinea-pig isolated atria.

Abstract:

:1. The effect of adenosine triphosphate (ATP) and its stable analogues, alpha, beta-methylene-ATP and beta, gamma-methylene-ATP, on the efferent function of capsaicin-sensitive non-adrenergic, non-cholinergic (NANC) nerves was tested in guinea-pig isolated atria. 2. Transmural nerve stimulation of atria isolated from reserpine-pretreated guinea-pigs, in the presence of 1 microM atropine and 0.3 microM CGP 20712A, induced a transient positive inotropic effect attributable to calcitonin gene-related peptide (CGRP) release from NANC nerve endings. 3. ATP (1-30 microM) concentration-dependently reduced the cardiac response to transmural nerve stimulation, without affecting the inotropic response to 10 nM exogenous CGRP. The inhibitory effect of ATP was competitively antagonized by the P1-purinoceptor antagonist, 8-phenyltheophylline (8-PT, 1 microM), but was unaffected by the P2-purinoceptor antagonist, suramin (100 microM). 4. beta, gamma-methylene-ATP in the same concentration range as ATP, inhibited the cardiac response to transmural nerve stimulation. The inhibitory effect of beta, gamma-methylene ATP was antagonized by 1 microM 8-PT. The desensitizing agonist for P2-purinoceptors, alpha, beta-methylene ATP did not induce any inhibitory effect either on the cardiac response to transmural nerve stimulation or on the inhibitory effect curve for ATP. 5. The inhibitory effect of ATP on the NANC neurotransmission was inconsistently modified in the presence of 10 microM alpha, beta-methylene-adenosine diphosphate, an inhibitor of the 5'-ectonucleotidases. 6. These results demonstrate that ATP modulates the efferent function of cardiac NANC nerve endings through prejunctional inhibitory receptors belonging to the P1 type. The metabolic conversion of ATP to adenosine does not seem to be a pre-requisite for the ATP agonist activity.

journal_name

Br J Pharmacol

authors

Rubino A,Amerini S,Ledda F,Mantelli L

doi

10.1111/j.1476-5381.1992.tb09011.x

subject

Has Abstract

pub_date

1992-03-01 00:00:00

pages

516-20

issue

3

eissn

0007-1188

issn

1476-5381

journal_volume

105

pub_type

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