Interactions between cyclic AMP and inositol phosphate transduction systems in astrocytes in primary culture

Astroglial cells in primary culture possess receptors with cyclic AMP and inositol phosphates (IP) as second messengers. The beta-receptor agonist, isoproterenol induces an increase in the accumulation of cyclic AMP, the alpha 2-receptor agonist clonidine inhibits the isoproterenol-induced accumulation of cyclic AMP, while the alpha 1-receptor agonist phenylephrine acts only on the inositol phosphate system. 5-Hydroxytryptamine (5-HT) stimulates, the formation of inositol phosphate, while isoproterenol and clonidine per se do not affect the inositol phosphate system. In the present paper the possibility of interactions between the cyclic AMP and the inositol phosphate transduction systems were investigated. In the presence of 10(-5) M 5-HT, in itself ineffective on the formation of cyclic AMP, isoproterenol stimulated the accumulation of cyclic AMP far more than in the absence of 5-HT. The potentiation was blocked by the 5-HT2 receptor antagonist ketanserin. On the other hand, there were no indications for a beta-receptor influence on the 5-HT-induced inositol phosphate formation. Stimulation of the alpha 2-receptor did not induce accumulation of inositol phosphate but significantly potentiated 5-HT2-receptor transduction, as measured by hydrolysis of phosphoinositide and formation of inositol phosphate. Stimulation by 5-HT also increased the formation of inositol phosphate after adrenergic stimulation and this effect was found to be synergistic at certain concentrations of adrenergic agonists. In addition, there was a statistically significant accumulation of cyclic AMP in the presence of both 5-HT and phenylephrine, none of which stimulated cyclic AMP alone. The results suggest specific interactions between the cyclic AMP and inositol phosphate systems on cultured astroglial cells.