Histamine Stimulation of Cyclic AMP Accumulation in Astrocyte-Enriched and Neuronal Primary Cultures from Rat Brain

Abstract

Histamine stimulates cyclic AMP accumulation in astrocyte-enriched and neuronal primary cultures from rat brain in the presence of the phosphodiesterase inhibitior isobutylmethylxanthine. The response in the astrocyte cultures (Emax = 304 .+-. 44% over basal, EC50 = 43 .+-. 5 .mu.M) was much higher than in neuronal cultures (Emax = 24 .+-. 2%, EC50 = 14 .+-. .mu.M). The histamine effect in astrocytes was competively inhibited by the H2 antagonists cimetidine (Ki = 1.1 .+-. 0.2 .mu.M) and ranitidine (Ki 46 .+-. 10 nM) but was insensitive to the H1 antagonist mepyramine (1 .mu.M). The two selective H2 agonists impromidine and dimaprit behaved as partial agonists and showed relative potencies (139 and 0.5, respectively) consistent with an interaction with H2 receptors. The more selective H1 agonist 2-thiazolylethylamine (0.01-1 mM) did not potentiate the response to impromidine (10 .mu.M). Thus, in contrast to what is generally observed in intact cell preparations from brain, the histamine-induced cyclic AMP accumulation in astroglial cells is mediated solely by H2 receptors. The small effect shown in neuronal cultures also appears to be mediated by H2 receptors.