Involvement of adenylate cyclase and protein kinase C in the alpha 2-adrenoceptor-mediated inhibition of noradrenaline and 5-hydroxytryptamine release in rat hypothalamic slices.

Naunyn-Schmiedeberg's Archives of Pharmacology
R RamdineS Z Langer

Abstract

In superfused rat hypothalamic slices prelabelled with [3H]-noradrenaline, the alpha 2-adrenoceptor agonist UK 14304 inhibited in a concentration-dependent manner the electrically-evoked release of tritium. This inhibition was antagonized by the alpha 2-adrenoceptor blocking agent idazoxan, which by itself increased the electrically-evoked tritium overflow. Exposure to forskolin, an adenylate cyclase activator, increased the electrically-evoked release of [3H]-noradrenaline. In the presence of forskolin (1 mumol/l), both the inhibitory effect of UK 14304 and the increasing effect of idazoxan on the electrically-evoked release of [3H]-noradrenaline were less pronounced than in the absence of the adenylate cyclase activator. Exposure to forskolin and to the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine shifted to the right the concentration-effect curve for UK 14304 in a similar manner as that observed in the presence of forskolin alone. Exposure to phorbol-12,13-dibutyrate (0.01-10 mumol/l), a drug which activates protein kinase C, increased the electrically-evoked release of [3H]-noradrenaline. In the presence of phorbol-12,13-dibutyrate (0.1 and 1 mumol/l), the concentration effect curve for UK 14304 on tritium overf...Continue Reading

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Citations

Jan 1, 1990·Annals of the New York Academy of Sciences·G HerttingC Allgaier

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