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Phorbol Esters Enhance Neurotransmitter‐Stimulated Cyclic AMP Production in Rat Brain Slices
Author(s) -
Karbon E. W.,
Shenolikar S.,
Enna S. J.
Publication year - 1986
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.1471-4159.1986.tb00796.x
Subject(s) - forskolin , protein kinase c , second messenger system , adenylate kinase , neurotransmitter , protein kinase a , phosphodiesterase , phorbol , medicine , endocrinology , ibmx , biology , phosphodiesterase inhibitor , stimulation , cyclic nucleotide phosphodiesterase , receptor , biochemistry , signal transduction , phosphorylation , enzyme
The effect of phorbol esters on cyclic AMP production in rat CNS tissue was examined. Using a prelabeling technique for measuring cyclic AMP accumulation in brain slices, it was found that phorbol 12‐myristate, 13‐acetate (PMA) enhanced the cyclic AMP response to forskolin and a variety of neurotransmitter receptor stimulants while having no effect on second messenger accumulation itself. A short (15‐min) preincubation period with PMA was required to obtain maximal enhancement, whereas the augmentation was lessened by prolonged exposure (3 h) to the phorbol. The response to PMA was concentration dependent (EC 50 = 1 μ M ) and regionally selective, being most apparent in forebrain, and was not influenced by removal of extracellular calcium or by inhibition of phosphodiesterase or phospholipase A 2 . Only those phorbols known to stimulate protein kinase C augmented the accumulation of cyclic AMP. Moreover, the membrane substrates phosphorylated by endogenous C kinase and by a partially purified preparation of this enzyme were similar. The results suggest that phorbol esters, by activating protein kinase C, modify the cyclic AMP response to brain neurotransmitter receptor stimulation in brain by influencing a component of the adenylate cyclase system beyond the transmitter recognition site.