Adrenergic activation of glycogen phosphorylase in primary culture diabetic cardiomyocytes.
The basis of catecholamine-induced activation of glycogen phosphorylase was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. Cells derived from diabetic animals exhibited a hypersensitive response to epinephrine stimulation that was apparent 3 h after cell isolation and was further enhanced on maintenance of the myocytes in culture for 24 h. Normal cells initially lacked the hypersensitive response to epinephrine stimulation, although on maintenance of these cells in culture for 24 h, the hypersensitive response was acquired in vitro. To assess alpha- and beta-adrenergic mediation of the response, normal and diabetic cardiomyocytes were incubated with propranolol, a beta-blocker, before direct alpha 1-receptor stimulation with phenylephrine. Both normal and diabetic myocytes failed to undergo activation of phosphorylase in 3- or 24-h cell cultures. In addition, the effects of epinephrine on phosphorylase activation were completely inhibited by propranolol, whereas prazosin, an alpha-blocker, was unsuccessful. The present data suggest that the hypersensitive response of glycogen phosphorylase in normal and diabetic cardiomyocytes is solely mediated through beta-adrenergic receptor activation.
Buczek-Thomas
J A
JA
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01655.
Jaspers
S R
SR
Miller
T B
TB
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010656:Phenylephrine / Q000494:pharmacology*; D006005:Phosphorylases / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D010656:Phenylephrine; D011433:Propranolol; D006005:Phosphorylases; D011224:Prazosin; D004837:Epinephrine