Involvement of central cholinergic muscarinic receptors and histamine H1 receptors in hyperglycemia induced by prostaglandin F2 alpha in rats.

We studied the effects of the histamine H1 receptor antagonists diphenhydramine and pyrilamine, the H2 receptor antagonist ranitidine and the muscarinic receptor antagonist atropine injected into the third cerebral ventricle on prostaglandin F2 alpha (PGF2 alpha)-induced hyperglycemia in anesthetized fed rats. The concomitant injection of diphenhydramine (1 x 10(-8), 5 x 10(-8) mol) with 50 micrograms PGF2 alpha significantly suppressed the increase in hepatic plasma glucose concentrations induced by PGF2 alpha. The concomitant injection of 1 x 10(-8) mol pyrilamine with 50 micrograms PGF2 alpha did not suppress the above-mentioned parameter, while 5 x 10(-8) mol pyrilamine significantly suppressed it. Diphenhydramine suppressed the PGF2 alpha-induced hyperglycemia to a greater extent than did pyrilamine. In contrast, concomitant injection of the H2 receptor antagonist ranitidine (1 x 10(-8), 5 x 10(-8) mol) did not suppress the hyperglycemia induced by PGF2 alpha. The concomitant injection of 5 x 10(-8) mol diphenhydramine or pyrilamine with 50 micrograms PGF2 alpha significantly suppressed the increase in plasma epinephrine induced by PGF2 alpha, but the same dose of ranitidine had no effect. The concomitant injection of atropine (5 x 10(-8), 5 x 10(-7) mol) with 50 micrograms PGF2 alpha significantly suppressed the increase in hepatic plasma glucose and epinephrine induced by PGF2 alpha. These findings demonstrate that PGF2 alpha-induced hyperglycemia is mediated by the muscarinic receptors of cholinoceptive neurons and in part by H1 receptors in the central nervous system.