Abstract

Isoproterenol (ISO)-induced relaxation of oxytocin-induced Ca(++)-independent contraction of the rat uterus was examined. Oxytocin induced Ca(++)-dependent phasic contraction in a solution containing Ca++ (normal contraction) and Ca(++)-independent sustained contraction in Ca(++)-free solution (Ca(++)-free contraction). Both contractions were completely suppressed by cyclic AMP-elevating relaxants such as ISO, dibutyryl cyclic AMP and forskolin. Moreover, the ISO concentration needed to inhibit the Ca(++)-free contraction was lower than that needed for normal contraction, although the relaxing effect of dibutyryl cyclic AMP and forskolin during Ca(++)-free contraction was not significantly different from that during Ca(++)-dependent contraction. The ISO-induced relaxation of the uterus in Ca(++)-free solution may involve three mechanisms. The first is cyclic AMP-dependent relaxation shown by high concentrations (more than 1 nM) of ISO. The second is stabilization via K+ channels by intermediate concentrations (10 pM to 1 nM) of ISO. These two actions appear to be mediated through beta-1 adrenoceptors. The third is, however, via an unknown subtype of adrenoceptor stimulated by extremely low concentrations (1 pM to 10 pM) of ISO. All of these relaxing mechanisms are independent of Ca++.