CYCLIC GMP-DEPENDENT PROTEIN-KINASE ACTIVATION MEDIATES INHIBITION OF CATECHOLAMINES SECRETION AND CA2+ INFLUX IN BOVINE CHROMAFFIN CELLS

被引：21

作者：

RODRIGUEZPASCUAL, F ^{[1
]}

MIRASPORTUGAL, MT ^{[1
]}

TORRES, M ^{[1
]}

机构：

[1] UNIV COMPLUTENSE MADRID, FAC VET, DEPT BIOQUIM, E-28040 MADRID, SPAIN

来源：

NEUROSCIENCE | 1995年 / 67卷 / 01期

关键词：

D O I：

10.1016/0306-4522(95)00035-H

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The effects of the membrane-permeable cGMP analogue, 8-bromoguanosine 3':5'-cyclic monophosphate on acetylcholine-evoked catecholamine secretion and cytosolic calcium increases were studied in chromaffin cells from the bovine adrenal gland. Preincubation with 100 mu M 8-bromoguanosine 3':5'-cyclic monophosphate during 10 and 30 min decreased the acetylcholine-evoked catecholamine release by 16 +/- 3% and 27 +/- 5%, respectively. The cytosolic calcium increases triggered by acetylcholine and 30 mM KCl were also inhibited by 30 min of preincubation with this compound by 27 +/- 4 and 34 +/- 2%, respectively. Changes in membrane potential induced by acetylcholine and KCl were not affected by preincubation with 8-bromoguanosine 3':5'-cyclic monophosphate. The cyclic GMP-dependent protein kinase inhibitor N-[2-(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride- at 1 mu m abolished the inhibitory effect of 8-bromoguanosine 3':5'-cyclic monophosphate on acetylcholine-evoked calcium increase. By contrast, a potent and selective inhibitor against cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide did not block the 8-bromoguanosine 3':5'-cyclic monophosphate effect. Additionally, 8-bromoguanosine 3': 5'cyclic monophosphate stimulated histone F-2b phosphorylation by a partial purified cGMP-dependent protein kinase from chromaffin cells. The extent of histone phosphorylation was reduced by N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride and 8-(4-chlorophenylthio)-guanosine 3':5'-cyclic monophosphorothioate, Rp-isomer, a specific inhibitor against cyclic GMP-dependent protein kinase, whereas it was not modified by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide. The results suggest that the inhibitory effects of 8-bromoguanosine 3':5' cyclic monophosphate on chromaffin cells are mediated through the activation of cGMP-dependent protein kinase. The target for this kinase does not appear to be either the nicotinic receptor or potassium channels, but it could be proteins which participate in Ca2+ influx or in the maintenance of calcium levels in chromaffin cells.

引用

页码：149 / 157

页数：9

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