MODULATION OF THE DIHYDROPYRIDINE-INSENSITIVE CA2+ INFLUX BY 8-BROMO-GUANOSINE-3'/5'-MONOPHOSPHATE, CYCLIC (8-BR-CGMP) IN BOVINE ADRENAL CHROMAFFIN CELLS

Pretreatment of chromaffin cells with the permeable analogue of cGMP, 8-Br-cGMP (100 mu M), leads to a reduction (35%) of depolarization-evoked intracellular calcium concentration ([Ca2(+)](i)) increases. There is evidence that bovine adrenal chromaffin cells are provided with both dihydropyridine-sensitive and -resistant voltage-sensitive Ca2+ influx pathways. Combined incubations with nifedipine 10 mu M and 8-Br-cCMP reduced KCl-evoked intracellular Ca2+ concentration to a greater extent that each compound separately. Moreover, 8-Br-cGMP failed to affect the [Ca2+](i) transient induced by the L-type Ca2+ channel agonist Bay K 8644 (1 mu M) under conditions of low depolarization. Neomycin (0.2 mM) and omega-AgaToxin-IVA (AgTx) (1 mu M) inhibited the calcium transient to a similar extent, and this inhibition was not enhanced by the presence of 8-Br-cGMP. It is concluded that 8-Br-cGMP modulated the dihydropyridine-insensitive Ca2+ influx pathway in the chromaffin cell.