Ralevic V, Burnstock G
Department of Anatomy and Developmental Biology, University College London, U.K.
Eur J Pharmacol. 1990 Jan 17;175(3):291-9. doi: 10.1016/0014-2999(90)90567-p.
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.
