title: Postjunctional synergism of noradrenaline and adenosine 5'-triphosphate in the mesenteric arterial bed of the rat.
abstract: 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.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, U.K.
authors.forename: V
authors.initials: V
authors.lastname: Ralevic
authors.forename: G
authors.initials: G
authors.lastname: Burnstock
mesh_terms: 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
chemical_list: D011942:Receptors, Adrenergic, alpha; D011983:Receptors, Purinergic; D012701:Serotonin; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine