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 H-1 receptor antagonists diphenhydramine and pyrilamine, the H-2 receptor antagonist ranitidine and the muscarinic receptor antagonist atropine injected into the third cerebral ventricle on prostaglandin F2alpha (PGF2alpha)-induced hyperglycemia in anesthetized fed rats. The concomitant injection of diphenhydramine (1 x 10(-8), 5 x 10(-8) mol) with 50 mug PGF2alpha significantly suppressed the increase in hepatic plasma glucose concentrations induced by PGF2alpha. The concomitant injection of 1 x 10(-8) mol pyrilamine with 50 mug PGF2alpha did not suppress the above-mentioned parameter, while 5 x 10(-8) mol pyrilamine significantly suppressed it. Diphenhydramine suppressed the PGF2alpha-induced hyperglycemia to a greater extent than did pyrilamine. In contrast, concomitant injection of the H-2 receptor antagonist ranitidine (1 x 10(-8), 5 x 10(-8) mol) did not suppress the hyperglycemia induced by PGF2alpha. The concomitant injection of 5 x 10(-8) mol diphenhydramine or pyrilamine with 50 mug PGF2alpha significantly suppressed the increase in plasma epinephrine induced by PGF2alpha, 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 mug PGF2alpha significantly suppressed the increase in hepatic plasma glucose and epinephrine induced by PGF2alpha. These findings demonstrate that PGF2alpha-induced hyperglycemia is mediated by the muscannic receptors of cholinoceptive neurons and in part by H-1 receptors in the central nervous system.