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Protein Kinase C and Phospholipase C Mediate α‐ and β‐Adrenoceptor Intercommunication in Rat Hypothalamic Slices
Author(s) -
Petitti Nicolas,
Etgen Anne M.
Publication year - 1991
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.1471-4159.1991.tb08196.x
Subject(s) - protein kinase c , phospholipase c , endocrinology , protein kinase a , phenylephrine , medicine , prazosin , phorbol , biology , long term potentiation , chemistry , signal transduction , receptor , antagonist , biochemistry , kinase , blood pressure
These experiments examined the mechanism by which phenylephrine enhances β‐adrenoceptor‐stimulated cyclic AMP formation in rat hypothalamic and preoptic area slices. To this end we manipulated phospholipase C, phospholipase A 2 , and protein kinase C activity in slices and assessed the effects of these manipulations on phenylephrine augmentation of isoproterenol‐stimulated cyclic AMP generation. Since previous work indicated that estrogen enhances the α 1 ‐component of cyclic AMP formation, we examined slices from both gonadectomized and estrogen‐treated animals. The α 1 ‐antagonist prazosin eliminated phenylephrine augmentation of the β‐response, suggesting that α 1 ‐adrenergic receptors mediate the potentiation of cyclic AMP formation. Inhibition of protein kinase C by H7 attenuated the α 1 ‐augmentation of β‐stimulated cyclic AMP formation. Staurosporine, a more potent protein kinase C inhibitor, completely abolished the α 1 ‐augmenting response. In addition, phenylephrine potentiation of the isoproterenol response was not observed if protein kinase C was first stimulated directly with a synthetic diacylglycerol (1‐oleoyl‐2‐acetyl‐ sn ‐glycerol) or phorbol ester (phorbol 12, 13‐dibutyrate). Neomycin, an inhibitor of phospholipase C, decreased α 1 ‐receptor enhancement of β‐stimulated cyclic AMP formation, whereas quinacrine, an inhibitor of phospholipase A 2 , did not. The data suggest that the postreceptor mechanism involved in α 1 ‐adrenergic receptor potentiation of cyclic AMP generation in hypothalamic and preoptic area slices includes activation of phospholipase C and protein kinase C.