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, α,β-methylene ATP α,β-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 α,β-meATP. Conversely, suprathreshold doses of NA potentiated contractions evoked by α,β-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 α 1-adrenoceptors and the P 2X-purinergic receptors since: (i) the potentiation of the contractile response to NA by ATP was mimicked by α,β-meATP but not by adenosine and (ii) pressor responses to 5-HT or to KCl were not affected by α,β-meATP. Possible mechanisms for this postjunctional synergism are discussed.