Involvement of Central Cholinergic Muscarinic Receptors and Histamine H₁ Receptors in Hyperglycemia Induced by Prostaglandin F₂α in Rats

Abstract

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 F₂α (PGF₂α)-induced hyperglycemia in anesthetized fed rats. The concomitant injection of diphenhydramine (1 × 10^–8, 5 × 10^–8 mol) with 50 µg PGF₂α significantly suppressed the increase in hepatic plasma glucose concentrations induced by PGF₂α The concomitant injection of 1 × 10^–8 mol pyrilamine with 50 µg PGF₂α did not suppress the above-mentioned parameter, while 5 × 10^-8 mol pyrilamine significantly suppressed it. Diphenhydramine suppressed the PGF₂α-induced hyperglycemia to a greater extent than did pyrilamine. In contrast, concomitant injection of the H₁ receptor antagonist ranitidine (1 × 10^–8, 5 × 10^–8 mol) did not suppress the hyperglycemia induced by PGF₂α. The concomitant injection of 5 × 10^–8 mol diphenhydramine or pyrilamine with 50 µg PGF₂α significantly suppressed the increase in plasma epinephrine induced by PGF₂α, but the same dose of ranitidine had no effect. The concomitant injection of atropine (5 × 10^–8, 5 × 10^–7 mol) with 50 µg PGF₂α significantly suppressed the increase in hepatic plasma glucose and epinephrine induced by PGF₂α. These findings demonstrate that PGF₂α-induced hyperglycemia is mediated by the muscarinic receptors of cholinoceptive neurons and in part by H₁ receptors in the central nervous system.

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“…Subsequent studies revealed that hyperglycemia induced by injection of PGF2α into the ventricle is as a result of an increase in epinephrine secretion from the adrenal medulla, muscarinic receptors of cholinoceptive neurons and, in part, by H1 receptors in the central nervous system. [97] , [98] ). These studies suggest that PG system plays a role in the development of hyperglycemia both by peripheral (by inducing inflammation and insulin resistance) and by central actions.…”