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, a,f-methylene-ATP and 3,Bymethylene-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 UM atropine and 0.3 pM CGP 20712A, induced a transient positive inotropic effect attributable to calcitonin gene-related peptide (CGRP) release from NANC nerve endings.3 ATP (1-30OpM) concentration-dependently reduced the cardiac response to transmural nerve stimulation, without affecting the inotropic response to 10nm exogenous CGRP. The inhibitory effect of ATP was competitively antagonized by the P1-purinoceptor antagonist, 8-phenyltheophylline (8-PT, 1pM), but was unaffected by the P2-purinoceptor antagonist, suramin (100pgM). 4 fl,y-Methylene-ATP in the same concentration range as ATP, inhibited the cardiac response to transmural nerve stimulation. The inhibitory effect of fi,y-methylene ATP was antagonized by 1 yM 8-PT. The desensitizing agonist for P2-purinoceptors, a,#-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 10pM axJ-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.

Evidence for P2‐purinoceptor‐mediated inhibition of noradrenaline release in rat brain cortex

“…While our results support the notion of a common presynaptic nucleoside and nucleotide receptor, the potent antagonist effect of DPCPX identifies the receptor in rat brain cortex as Al. In this, the rat brain cortex noradrenergic axons would agree with the noradrenergic axons of rabbit brain cortex, rat vas deferens and mouse vas deferens (von Kiugelgen et al, 1992a;1994a;Fuder & Muth, 1993;; compare the studies on non-noradrenergic neurones by Moody et al, 1984;Wiklund et al, 1985;Rubino et al, 1992;Cunha et al, 1994). Adenine nucleotides also activate Al-receptors in non-neural cells (Bailey et al, 1992).…”

Effect of ATP and its analogs on contractility of rat myocardium during ontogeny

“…However, direct action of ATP on the heart via its own P2-receptors irrespective on its degradation to adenosine was proven. Under conditions of blockade of P1-receptors, exogenous ATP produces a positive inotropic effect in guinea pig left artium probably via activation of P2Y-receptors [6]. ATP increases contractility of guinea pig cardiomyocytes by 26% [7].…”

“…The effects of ATP and 2MeSATP on contraction force and duration were calculated in percentage of the control (100%). To block P1-receptors, we used 8-phenyltheophylline in a concentration of 10 -3 M [6].…”

Role of P2X and P2Y receptors in rat myocardial contractility during ontogeny

“…By contrast, 2MeSATP is a stable agonist of cardiac P2X and P2Y receptors [7]. In most in vitro experiments, ATP is not the strongest agonist; it is weaker than 2MeSATP: 2MeSATP>ATP>α,β-MeSATP.…”

“…Changes in the contraction force in response to 2MeSATP application were calculated in percents of initial value (100%). PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, Sigma), a selective and stable antagonist of P2X receptors, was used in a concentration of 10 -5 M [7]; P2Y receptors were blocked with anthraquinone derivative reactive blue-2 (RB-2, 1.5 µM) [3].…”