Postjunctional synergism of noradrenaline and adenosine 5'-triphosphate in the mesenteric arterial bed of the rat.
The ability of purines to modify responses to exogenous noradrenaline (NA) was investigated using the isolated perfused rat mesenteric bed. ATP, at subthreshold doses and above-threshold doses, produced a potentiation of vasoconstrictor responses to NA while adenosine was without effect. The stable analogue of ATP, alpha,beta-methylene ATP alpha,beta-meATP, at subthreshold and above-threshold doses also enhanced pressor responses to NA (to a greater extent than ATP). This potentiation caused a shift to the left of the dose-response curve, with no increase in the maximum response. Pressor responses to 5-hydroxytryptamine (5-HT) and to potassium chloride (KCl), however, were not affected by alpha,beta-meATP. Conversely, suprathreshold doses of NA potentiated contractions evoked by alpha,beta-meATP, but no potentiation was observed using subthreshold doses of NA. These results demonstrate a postjunctional synergistic action between NA and ATP which appeared to be specific for the alpha 1-adrenoceptors and the P2x-purinergic receptors since: (i) the potentiation of the contractile response to NA by ATP was mimicked by alpha,beta-meATP but not by adenosine and (ii) pressor responses to 5-HT or to KCl were not affected by alpha,beta-meATP. Possible mechanisms for this postjunctional synergism are discussed.
Ralevic
V
V
Department of Anatomy and Developmental Biology, University College London, U.K.
Burnstock
G
G
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011983:Receptors, Purinergic / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011983:Receptors, Purinergic; D012701:Serotonin; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine