Dual contractile effects of ATP released by field stimulation revealed by effects of α,β‐methylene ATP and suramin in rat tail artery

Abstract

1 The field stimulation-induced release of endogenous ATP and noradrenaline (NA) and contractile response in rat isolated tail artery were examined. The release of ATP was studied by extracellular electrophysiological recording and that of NA by a novel voltammetrical technique. The effects of the P2-purinceptor antagonist, suramin, on these parameters were compared with those of a,-methylene ATP, a P2x-purinoceptor desensitizing agent. 2 Neither a,-methylene ATP (101 M) nor suramin (100-500I1M) had significant effects on the extracellularly recorded nerve terminal action potential but both abolished the ATP-induced excitatory junction current caused by stimulation at 0.1 Hz. Neither agent affected significantly the voltammetrically measured release of NA induced by 10 or 100 pulses at 20 Hz. 3 Combined blockade of both postjunctional a,-and a2-adrenoceptors by prazosin and yohimbine (both 0.1 LM) profoundly depressed the contractile response to 10 pulses at 20 Hz. The small and fast residual contraction in the presence of these agents was abolished by a,$-methylene ATP (10fM) and inhibited by suramin in a concentration-dependent manner (10-500IAM; IC-% 75 AM) and was hence probably caused by ATP or a related nucleotide.4 When added first, a,-methylene ATP (10ILM) or suramin (100-500 M) delayed the onset and enhanced the amplitude of the neurogenic contraction. This enhanced response was abolished by further addition of prazosin and yohimbine (both 0.1 tiM). S The K+ channel blocker, tetraethylammonium (10mM), dramatically enhanced the contractile response to 100 pulses at 1 Hz and caused it to become diphasic. Addition of a,p-methylene ATP (10 gM) or suramin (100-500 p.M) abolished the large initial twitch component of this contraction and depressed the tonic phase.6 Like a,p-methylene ATP, suramin (500#iM) had no effect on the contraction caused by exogenous NA (1O nM-100 ltM) or KCI (60 mM); both agents almost abolished the contraction caused by ATP (100 fLM).

P2X Receptor Immunoreactivity in Different Arteries from the Femoral, Pulmonary, Cerebral, Coronary and Renal Circulations

“…This range of expression of P2X receptors may explain in part the differences in the magnitude of P2X receptor-mediated responses between different arteries, as substantial P2X receptor-mediated neurogenic vasoconstriction is most commonly seen in small and medium arteries [9, 11, 55, 56]. In larger arteries, the P2X receptor-mediated neurogenic component is usually small [10, 11]. This pattern is consistent with the relatively lower innervation density in larger arteries [57]and indicates that there is a correlation between the level of innervation, P2X receptor expression and functional responsiveness.…”

“…9 and 10], (2) the diameter of the artery [11]and (3) the parameters of stimulation [12, 13]. For example, in small arterioles, the response to sympathetic nerve stimulation is mediated solely by P2X receptors [9], whereas in the large caudal (tail) artery, the adrenergic component dominates [10]. One possibility is that the range of responses may reflect an heterogeneity in the P2X receptor populations or density expressed by different arteries.…”

“…The relative importance of the purinergic component is dependent on (1) the type of artery [compare ref. 9 and 10], (2) the diameter of the artery [11]and (3) the parameters of stimulation [12, 13]. For example, in small arterioles, the response to sympathetic nerve stimulation is mediated solely by P2X receptors [9], whereas in the large caudal (tail) artery, the adrenergic component dominates [10].…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…The EJPs were later shown to be due to ATP released as a cotransmitter from sympathetic nerves, because they were blocked by desensitization of P2X receptors by a,b-meATP (Sneddon and Burnstock, 1984b;Neild and Kotecha, 1986). Suramin, a P2 receptor antagonist, was also shown to block the ATP component of sympathetic neurotransmission of the rat tail artery (Bao and Stjärne, 1993). Coreleased NA and ATP from sympathetic nerves supplying the rail artery have synergistic postjunctional contractile actions on the smooth muscle (Johnson et al, 2001;Johnson, 2010).…”

Cardiovascular/Respiratory Control

“…PRA in group I was higher than in group H 123P (251'5 ± 31'6 vs. 78'0 ± 6'2 ngAI ml-1 h -t, P < 0'01), and both were elevated compared with the Cont group (2'8 ± 0'3 ngAI ml-1 h- In vitro studies have indicated that the nature of neuroeffector transmission is influenced by the pattern of sympathetic discharges. Synchronous and asynchronous models of sympathetic activity have been used to study neuroeffector transmission in the caudal ventral artery (CV A) of the rat in vitro using either electrical stimulation (synchronous, Bao & Stjarne, 1993) or ciguatoxin (asynchronous, Brock et al 1997). Using a focal recording technique, we have previously shown in vivo that the discharges of single sympathetic postganglionic neurones (PGNs) innervating the CV A are rhythmical (dominant rhythm: T-rhythm, Johnson & Gilbey, 1996).…”