Difference in the mechanism of action of alpha-adrenergic agonists and vasopressin or angiotensin II in stimulating hepatic glycogenolysis; a role of extracellular calcium concentration.
The role of extracellular calcium in hormone-induced glycogenolysis was examined in a rat liver perfusion system by manipulating the perfusate calcium concentration and by using calcium antagonistic drugs. When the perfusate contained 1 mM CaCl2, 5 microM phenylephrine, 20 nM vasopressin, and 10 nM angiotensin II caused a persistent increase in glucose output and phosphorylase activity as well as a transient increase in 45Ca efflux from 45Ca preloaded liver. Verapamil hydrochloride (20-100 microM) inhibited the activation of glucose output by these hormones in a dose-dependent manner. This inhibitory effect was also associated with the inhibition of hormone-induced activation of phosphorylase and 45Ca efflux. In the absence of CaCl2 in the perfusate, the glycogenolytic effect of phenylephrine and its inhibition by verapamil were obtained equally as in the presence of CaCl2. However, the effects of vasopressin and angiotensin II were markedly attenuated and were not inhibited any further by verapamil. The substitution of diltiazem hydrochloride for verapamil produced essentially identical results. Cyclic AMP concentrations in the tissue did not change under any of these test conditions. The results indicate that the glycogenolytic effect of alpha-adrenergic agonists depends on intracellular calcium but those of vasopressin and angiotensin II on extracellular calcium, and support the concept that calcium antagonistic drugs inhibit the glycogenolytic effects of calcium-dependent hormones at least by inhibiting the mobilization of calcium ion from cellular pools.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D009712:Nucleotides, Cyclic / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D008112:Liver Glycogen; D009712:Nucleotides, Cyclic; D000804:Angiotensin II; D001127:Arginine Vasopressin; D010656:Phenylephrine; D014700:Verapamil; D006005:Phosphorylases; D005947:Glucose; D002118:Calcium