Effects of adenosine receptor agonists on induction of contractions to phenylephrine of guinea-pig aorta mediated via intra- or extracellular calcium.
The vasorelaxant actions of adenosine and its analogue, 5'-(N-ethylcarboxamido)-adenosine (NECA), were investigated in guinea-pig isolated aortic rings by addition to the tissue prior to induction of a contraction by the alpha1-adrenoceptor agonist phenylephrine (PE, 3x10(-6) M). The effect was calculated from the ratio (C2/C1) of the contraction to PE before (C1) and in the presence of adenosine or NECA (C2). This was compared with a control ratio obtained at the same time in which no vasorelaxant was present during C2. Experiments were performed in either "normal" or "Ca2+ -free" bathing medium. Both adenosine and NECA caused inhibition of contractions in "normal" and "Ca2+ -free" conditions, the latter indicating that the vasorelaxant action was due in part to inhibition of intracellular Ca2+ mobilization. To determine whether inhibition of influx of extracellular Ca2+ is a target for the vasorelaxation, contractions to PE were obtained in "normal" Ca2+ and in the presence of ryanodine (10(-5) M), which prevents the release of intracellular Ca2+. These contractions were inhibited by NECA indicating that stimulation of A2-receptors by NECA interferes with the influx of Ca2+ via the opening of receptor-operated Ca2+ channels (ROCs). This study has demonstrated that cell surface A2-receptor stimulation in the guinea-pig aorta inhibits phenylephrine-induced contractions by interfering with both the release of intracellular Ca2+ and the influx of extracellular Ca2+, presumably via ROCs.
Ford
W R
WR
Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, UK.
Broadley
K J
KJ
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D018047:Receptors, Purinergic P1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine; D002118:Calcium