ANGIOTENSIN-II RECEPTORS ARE COUPLED TO OMEGA-CONOTOXIN-SENSITIVE CALCIUM INFLUX IN BOVINE ADRENAL-MEDULLARY CHROMAFFIN CELLS

The contribution of an omega-conotoxin GVIA (omega-Cgtx)-sensitive Ca2+ influx pathway to the effects of angiotensin II (AII) receptor activation was examined in bovine adrenal medullary (BAM) cells. Pretreatment of BAM cells with 10(-6) M omega-Cgtx blocked stimulation of exocytosis by the degradation-resistant analogue, sarcosine1-angiotensin II (S1-AII). In contrast, omega-Cgtx had no effect on basal secretion, nor did it inhibit [H-3]norepinephrine and [P-32]ATP release in response to bradykinin, another phospholipase C-linked receptor agonist. Similarly, omega-Cgtx pretreatment inhibited the stimulation of Ca-45(2+) uptake by S1-AII, but did not affect the response to bradykinin. This selective inhibition did not appear to be due to blockade of AII receptors by omega-Cgtx, as the accumulation of H-3-labeled inositol phosphates in response to S1-AII was not inhibited. The peak S1-AII-stimulated increase in the intracellular free Ca2+ concentration (Ca(i)) in fura 2-loaded BAM cells also was not significantly reduced by omega-Cgtx (or by stimulating in nominally Ca2+-free buffer), indicating that this response is dependent on intracellular Ca2+ pools. However, a small omega-Cgtx-sensitive Ca(i) response was detected after depletion of intracellular Ca2+ pools with ionomycin. This study shows that AII receptors, but not bradykinin receptors, are linked to an omega-Cgtx-sensitive Ca2+ influx pathway in BAM cells.