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-ethylcarboxam ido)-adenosine (NECA), were investigated in guinea-pig isolated aortic ring s by addition to the tissue prior to induction of a contraction by the alph a(1)-adrenoceptor agonist phenylephrine (PE, 3 x 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 durin g C2. Experiments were performed in either "normal" or "Ca2+-free" bathing medium. Both adenosine and NECA caused inhibition of contractions in "norma l" 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 f or the vasorelaxation, contractions to PE were obtained in "normal" Ca2+ an d in the presence of ryanodine (10(-5) M), which prevents the release of in tracellular Ca2+. These contractions were inhibited by NECA indicating that stimulation of A,receptors by NECA interferes with the influx of Ca2+ via the opening of receptor-operated Ca2+ channels (ROCs). This study has demon strated that cell surface A(2)-receptor stimulation in the guinea-pig aorta inhibits phenylephrine-induced contractions by interfering with both the r elease of intracellular Ca2+ and the influx of extracellular Ca2+, presumab ly via ROCs. (C) 1999 Elsevier Science Inc. All rights reserved.