Mechanism of the central hyperglycemic action of histamine in mice.
The effect of i.c.v. administration of histamine (HA) on the plasma glucose level was examined in mice. HA (0.09-180 nmol) increased dose-dependently the plasma glucose level, 30 min after the injection. Even a low dose of 0.45 nmol produced a significant effect. The pretreatment with metoprine, an inhibitor of HA-N-methyltransferase, heightened the peak of the hyperglycemic response markedly and prolonged the duration. Systemic administration of the H1-receptor antagonists mepyramine (0.5-2 mg/kg), chlorpheniramine (1-4 mg/kg) and promethazine (1-4 mg/kg), inhibited dose-dependently the HA-induced hyperglycemia, whereas an H2-receptor antagonist, cimetidine (80 nmol i.c.v.), was without effect. The hyperglycemic response to HA disappeared in bilaterally adrenalectomized mice. Although the treatment of mice with metyrapone reduced the plasma corticosterone level to less than 15% of the control value, the hyperglycemic response to HA was still observed. After the administration of HA, there was a significant elevation of plasma norepinephrine levels. Increase in the plasma epinephrine was more marked than the norepinephrine response. Pretreatment with phentolamine (5 mg/kg i.p.) but not propranolol (15 mg/kg i.p.) inhibited the HA-induced hyperglycemia by about 50% and the combination of same doses of phentolamine and propranolol blocked the response completely. These results suggest that the central hyperglycemic effect of HA is produced mainly by an increase in the sympathetic outflow, followed by an increase in catecholamine secretion from the adrenal medulla. It is likely that the stimulation of H1, but not H2, receptors in the brain is involved in this response.
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002744:Chlorpheniramine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006943:Hyperglycemia / Q000139:chemically induced*; D051379:Mice; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D011398:Promethazine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011739:Pyrimethamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000378:metabolism; D013997:Time Factors
D001786:Blood Glucose; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; C006308:metoprine; D002744:Chlorpheniramine; D006632:Histamine; D011433:Propranolol; D011398:Promethazine; D011738:Pyrilamine; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine; D011739:Pyrimethamine; D010646:Phentolamine