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Noradrenaline Stimulation Unbalances the Phosphoinositide Cycle in Rat Cerebral Cortical Slices
Author(s) -
Claro Enrique,
Fain John N.,
Picatoste Fernando
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03492.x
Subject(s) - carbachol , medicine , endocrinology , phospholipase c , chemistry , phosphatidylinositol , inositol phosphate , stimulation , cholinergic , phosphatidic acid , inositol , biology , biochemistry , signal transduction , membrane , receptor , phospholipid
Muscarinic cholinergic and α 1 ‐adrenoceptor‐mediated stimulation of phosphoinositide hydrolysis in rat cerebral cortex were compared by measuring carbachol‐ and noradrenaline‐induced accumulation of various intermediates of the phosphoinositide cycle. Unlike carbachol, noradrenaline in the presence of guanosine 5′‐ O ‐(3‐thiotriphosphate) did not stimulate phospholipase C activity in brain cortical membranes. In cortical slices, the efficacy of noradrenaline to stimulate accumulation of 3 H‐inositol phosphates and [ 32 P]phosphatidic acid was 2.5 to threefold that of carbachol. However, noradrenaline was less effective than carbachol in stimulating accumulation of [ 3 H]CDP‐diacylglycerol and resynthesis of phosphatidylinositol. This was not due to calcium inhibition of CTP:phosphatidate cytidyltransferase or to different lithium requirements for carbachol‐ and noradrenaline‐stimulated accumulation of [ 3 H]CDP‐diacylglycerol. The noradrenaline‐induced unbalance of the phosphoinositide cycle, which was most apparent at relatively high concentrations of calcium (2.5 m M ) in the incubation buffer, was qualitatively reproduced with ionomycin. The use of the α 1a ‐subtype‐selective adrenoceptor antagonists WB4101 and 5‐methylurapidil revealed a single α 1a ‐like component mediating the effects of noradrenaline. Our results suggest that the primary mechanism for phospholipase C activation by brain α 1 adrenoceptors involves an increase in intracellular calcium concentration.