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.