Differential effects of D600, nifedipine and dantrolene sodium on excitation-secretion coupling and presynaptic beta-adrenoceptor responses in rat atria.

The stimulation-evoked release of tritium was measured from rat atria labelled with [3H]-noradrenaline. The calcium dependence of evoked release and the facilitation of this release via activation of presynaptic beta-adrenoceptors were examined using D600 (methoxyverapamil), nifedipine and dantrolene sodium. Both D600 and nifedipine at dose levels of 20 and 100 microM inhibited evoked release. Dantrolene (20, 100 microM) reduced release by 25%, the effect being maximal at 20 microM. In the presence of 20 nM isoprenaline, a facilitation of evoked release occurred, which was blocked by 0.1 microM (-)-propranolol. The facilitatory action of isoprenaline was abolished by omission of calcium from the buffer, or by D600 or nifedipine, (100 microM). In contrast, the response to isoprenaline was not modified by dantrolene (20, 100 microM). It is concluded that the evoked release of noradrenaline (NA) utilizes Ca from both intra- and extracellular sources and that isoprenaline increases NA secretion by promoting the depolarization-induced influx of Ca.