Effects of the novel dihydropyridine BAY-K-8644 on adrenomedullary catecholamine release evoked by calcium reintroduction.

Reintroduction of Ca ions to cat adrenal glands perfused at room temperature with Krebs solution lacking Ca and Mg, evoked a catecholamine secretory response that was directly proportional to the concentration of Ca reintroduced. This secretory response inactivated quickly, was abolished by nM concentrations of nifedipine and was potentiated dramatically by nM concentrations of BAY-K-8644. Excess Ca antagonized the inhibitory effects of nifedipine and this drug inhibited competitively the potentiating effects of BAY-K-8644. These data suggest 1st) that extracellular divalent cations deprivation activates specific Ca channels; 2nd) that the dihydropyridine BAY-K-8644 increases the release of catecholamines by Ca reintroduction by activating and/or delaying the inactivation of Ca channels; and 3rd) that the access of the dihydropyridine-type Ca agonist and antagonists to their "intra-channel" site of action requires the pre-activation of Ca channels.