Role of brain histamine H₁- and H₂-receptors in neostigmine-induced hyperglycemia in rats

We previously reported that when neostigmine, an inhibitor of acetylcholine esterase, was injected into the third cerebral ventricle, the concentration of hepatic venous plasma glucose was increased via central muscarinic receptors in anesthetized rats. To determine whether brain histamine receptors are involved in cholinergic system transmission with regard to central nervous system (CNS)-mediated glucoregulation, we examined the effects of the H₁ receptor antagonist pyrilamine and the H₂ receptor antagonist ranitidine on neostigmine-induced hyperglycemia in anesthetized rats. The injection of pyrilamine (5×10^-9-5×10^-7 mol) into the third cerebral ventricle suppressed hyperglycemia induced by intraventricular injection of neostigmine (1×10^-9 mol) in a dose-dependent manner. Injection of ranitidine (5×10^-9-5×10^-7 mol) into the third cerebral ventricle did not suppress the hyperglycemia induced by neostigmine, but enhanced it in a dose-dependent manner. These findings suggest that neostigmine-induced CNS-mediated hyperglycemia is transmitted by not only brain cholinergic muscarinic receptors but also in part by histamine H₁ receptors.