Inhibitory effect of [Asu1 . 7]-eel calcitonin on glucagon-induced glycogenolysis in perfused rat liver.
In an attempt to elucidate the mechanism by which calcitonin modulates glucose metabolism, the effect of elcatonin ([Asu1 . 7]-eel calcitonin), a potent synthetic eel calcitonin analogue, on hepatic glycogenolysis was investigated by use of perfused liver from fed rats. Elcatonin, as infused into the portal vein at concentrations between 10 mU/ml and 200 mU/ml did not affect glucose output into the hepatic venous effluent. At concentrations higher than 100 mU/ml, it inhibited the glycogenolysis stimulated by submaximal concentrations of glucagon which was perfused concurrently. This aspect of elcatonin effect was reproduced by synthetic salmon calcitonin. Though elcatonin showed a marked inhibition of the glycogenolytic activity induced by glucagon at or less than 5.7 X 10(-11) M, the inhibitory effect became undetectable when higher concentrations of glucagon were employed. Elcatonin did not inhibit the glycogenolysis induced by dibutyryl cyclic AMP at near (0.5 microM) or less than half-maximally effective (0.2 microM) concentrations. In addition, it did not inhibit the glycogenolytic activity half-maximally stimulated by alpha-adrenergic agonist (phenylephrine, 0.4 microM) or vasopressin (0.2 mU/ml). Elcatonin inhibited the cyclic AMP production of the tissue induced by glucagon infusion. These data indicate that elcatonin modulates hepatic glycogenolysis by preventing the glucagon effect at a step before cyclic AMP production and with an apparently competitive kinetics. In view of the concept that Ca++ is involved in the glycogenolytic effect of alpha-adrenergic agonist and vasopressin, the fact that elcatonin did not influence the action of these agents suggests that Ca++ fluxes are not involved in the elcatonin effect on liver.
D000818:Animals; D002116:Calcitonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D005934:Glucagon / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010656:Phenylephrine / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000502:physiology
D014667:Vasopressins; D010656:Phenylephrine; D006003:Glycogen; D002116:Calcitonin; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose; C012755:elcatonin