Phorbol esters enhance neurotransmitter-stimulated cyclic AMP production in rat brain slices.

Published

Journal Article

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 (EC50 = 1 microM) and regionally selective, being most apparent in forebrain, and was not influenced by removal of extracellular calcium or by inhibition of phosphodiesterase or phospholipase A2. 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.

Full Text

Duke Authors

Cited Authors

  • Karbon, EW; Shenolikar, S; Enna, SJ

Published Date

  • November 1986

Published In

Volume / Issue

  • 47 / 5

Start / End Page

  • 1566 - 1575

PubMed ID

  • 2876056

Pubmed Central ID

  • 2876056

International Standard Serial Number (ISSN)

  • 0022-3042

Language

  • eng

Conference Location

  • England