The inhibitory action of okadaic acid on mechanical responses in guinea-pig vas deferens

Abstract

Okadaic acid and nifedipine inhibited contractions induced by noradrenaline (NA), KCl and ATP in guinea-pig vas deferens. NA, KCl and ATP induced initial spike-like changes followed by a sustained increase in cytosolic Ca 2+ levels ([Ca 2+]cyt) and tension. Okadaic acid inhibited the sustained increments in [Ca 2+]cyt and muscle tension due to NA and ATP more than the initial spike-like changes, whereas nifedipine more strongly inhibited the initial spike changes. Okadaic acid also inhibited the KCl-induced contraction with only a small inhibition of the stimulated [Ca 2+]cyt. By contrast, nifedipine (10 −7 M) inhibited the increments in both [Ca 2+]cyt and muscle tension due to KCl. Okadaic acid markedly inhibited the maximal contractile response to Bay K 8644 but nifedipine only shifted the response curve to the right without affecting the maximum responses. In a Ca 2+-free medium containing EGTA and nifedipine, okadaic acid did not inhibit the residual phasic contractile response to NA (10 −4 M) but the contractile response to a subsequent addition of Ca 2+ (1.2 mM) was suppressed. These results suggest that, in guinea-pig vas deferens, okadaic acid has an inhibitory effect on smooth muscle contraction but not on the intracellular Ca 2+ mobilization. The inhibitory effect may be due to the inhibition of Ca 2+ influx and the possible interference of contractile elements.