[Hokkaido igaku zasshi] The Hokkaido journal of medical science
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Hokkaido Igaku Zasshi · Sep 1994
[Pharmacological studies on alterations in myocardial beta-adrenoceptors and their intracellular signal transduction in experimental diabetic rats].
The present study was undertaken to determine abnormalities which are responsible for the diminished functional responsiveness to beta-adrenoceptor stimulation in experimental diabetic rats. Rats were given an intravenous injection of 45mg/kg streptozotocin and hearts were removed from 4 to 6 weeks later. The positive inotropic effects of isoproterenol, norepinephrine and epinephrine were markedly depressed in diabetic rat papillary muscles. ⋯ To test this hypothesis, incorporation of [32P]-inorganic phosphate into phospholamban in sarcoplasmic reticulum was examined in Langendorff-perfused hearts. Isoproterenol (100nM) increased phosphorylation of phospholamban threefold in control hearts, but did not cause a significant change in the phosphorylation state in diabetic hearts. From these findings it is concluded that the decreased functional responses to cyclic AMP-increasing agents like beta-adrenoceptor agonists in diabetic hearts may be associated with impaired phosphorylation of cardiac regulatory phosphoproteins including phospholamban.