Effects of adenosine receptor agonists on induction of contractions to phenylephrine of guinea-pig aorta mediated via intra- or extracellular calcium

Abstract

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 α 1-adrenoceptor agonist phenylephrine (PE, 3 × 10 −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 “Ca 2+-free” bathing medium. Both adenosine and NECA caused inhibition of contractions in “normal” and “Ca 2+-free” conditions, the latter indicating that the vasorelaxant action was due in part to inhibition of intracellular Ca 2+ mobilization. To determine whether inhibition of influx of extracellular Ca 2+ is a target for the vasorelaxation, contractions to PE were obtained in “normal” Ca 2+ and in the presence of ryanodine (10 −5 M), which prevents the release of intracellular Ca 2+. These contractions were inhibited by NECA indicating that stimulation of A 2-receptors by NECA interferes with the influx of Ca 2+ via the opening of receptor-operated Ca 2+ channels (ROCs). This study has demonstrated that cell surface A 2-receptor stimulation in the guinea-pig aorta inhibits phenylephrine-induced contractions by interfering with both the release of intracellular Ca 2+ and the influx of extracellular Ca 2+, presumably via ROCs.