Myocardial calcium uptake in streptozotocin diabetic and control rats after dibutyryl-cAMP; alpha-adrenergic stimulation and calcium deprivation.
Previous studies have shown a decreased myocardial calcium uptake after beta-adrenergic stimulation with isoproterenol in isolated perfused hearts from streptozotocin diabetic rats. Abnormalities in the beta-receptor-adenylate cyclase system could explain this but in order to circumvene the receptor we studied the effect of the permeable cAMP analogue, dibutyryl-cAMP on this calcium uptake. A marked increase was seen in control hearts while no increase could be registered in diabetic hearts. Defects in the protein kinase phosphorylation system or in the protein kinase substrate in the sarcolemma are suggested. alpha-Adrenergic stimulation with phenylephrine, being a cAMP independent positive inotropic agent, was also tested but no increase in calcium uptake was seen in either control or diabetic hearts. This could be due to a different effect on calcium currents during action potential after alpha-stimulation compared to the beta-adrenergic effect. Reexposure to calcium after calcium deprivation leads to excessive myocardial calcium uptake (calcium paradox), but the increase was significantly smaller in diabetic hearts, suggesting a differential responsiveness to the damage induced by this procedure. Early biochemical abnormalities in the basement membrane or in the composition and calcium binding ability of the sarcolemma could possibly constitute a common final site for the defect myocardial calcium uptake after isoproterenol, db-cAMP and calcium deprivation in streptozotocin diabetic rats.
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D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002118:Calcium / Q000172:deficiency / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D003994:Bucladesine; D007545:Isoproterenol; D002118:Calcium