Effects of adrenergic blockers on central nervous system-mediated hyperglycemia in fed rats.
We studied the effect of adrenergic blockade on hepatic venous hyperglycemia and the activation of a hepatic glycogenolytic enzyme, phosphorylase-a, in response to cerebral cholinergic activation. Neostigmine was injected into the third cerebral ventricle of bilaterally adrenodemedullectomized (ADMX) rats, while somatostatin and insulin were administered intravenously. Hepatic venous plasma glucose concentrations and hepatic phosphorylase-a activity were measured. Intracerebroventricular injection of neostigmine (5 x 10(-8) mol) caused increases in hepatic venous glucose concentrations and hepatic phosphorylase-a activity. Both of these changes were prevented by intraperitoneal (IB) pretreatment with phentolamine (5 x 10(-7), 1 x 10(-6) mol) without the intervention of insulin secretion, but not by pretreatment with the alpha-adrenoreceptor antagonist phenoxybenzamine (1 x 10(-6) mol), the beta-adrenoreceptor antagonist propranolol (1 x 10(-6) mol), the alpha 1-antagonists prazosin or bunazosin (1 x 10(-6) mol), the alpha 2-antagonist yohimbine (1 x 10(-6) mol), or prazosin (5 x 10(-7) mol) plus yohimbine (5 x 10(-7) mol). These results suggest that phentolamine prevented brain-mediated hepatic glycogenolysis by a mechanism that may not be classified pharmacologically as involving either alpha 1- or alpha 2-receptors.
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Y
Y
Kunoh
A
A
Iguchi
K
K
Uemura
H
H
Miura
T
T
Tamagawa
T
T
Mano
K
K
Nonogaki
M
M
Gotoh
N
N
Sakamoto
D000315:Adrenalectomy; D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D006503:Hepatic Veins; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced / Q000209:etiology*; D007276:Injections, Intraventricular; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008297:Male; D009388:Neostigmine; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology*
D007328:Insulin; D013565:Sympatholytics; D009388:Neostigmine; D013004:Somatostatin; D010762:Phosphorylase a