Elsevier

Biochemical Pharmacology

Volume 58, Issue 5, 1 September 1999, Pages 881-885
Biochemical Pharmacology

Cardiovascular and Pulmonary Pharmacology
Diabetes-induced down-regulation of β1-adrenoceptor mRNA expression in rat heart

https://doi.org/10.1016/S0006-2952(99)00164-1Get rights and content

Abstract

The present study addressed the question of whether the number of myocardial β-adrenoceptors in rats with 4- to 6-week streptozotocin-induced diabetes is regulated in a transcriptional or translational manner. Radioligand binding experiments with [3H]CGP 12177 {4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one} showed that the density of β-adrenoceptors fell by 50% with no change in affinity in diabetic rat ventricular myocardium compared with age-matched control myocardium. The relative content of β1-adrenoceptor mRNA in diabetic myocardium also was reduced from the control level by 57%, as determined by northern blot analysis. The reductions in myocardial β-adrenoceptor number and β1-adrenoceptor mRNA observed in diabetes were prevented by insulin therapy. These data indicate that the diminished density of myocardial β-adrenoceptors in diabetes occurred, at least in part, at the mRNA level.

Section snippets

Induction of diabetes

Male Wistar rats, 8 weeks old and 180–200 g in body weight, were assigned, at random, to two groups. The rats were anesthetized lightly with diethyl ether, and the diabetic group received a single injection of streptozotocin (45 mg/kg) in citrate buffer into the tail vein. The control group received an equivalent volume of citrate buffer alone. Control and diabetic rats were caged separately but housed under identical conditions. Both groups of animals were given free access to food and water.

Results

β-Adrenoceptors in membrane fractions derived from ventricular myocardium of control and diabetic rats were identified using [3H]CGP 12177. The specific binding of [3H]CGP 12177 to myocardial membranes was saturable and showed high affinity in both control and diabetic groups (Fig. 1 A). Scatchard analysis of the data revealed that [3H]CGP 12177 bound to a single population of binding sites in both groups (Fig. 1B). The number of β-adrenoceptors was significantly lower in myocardial membranes

Discussion

In accordance with previous studies from this laboratory and others showing a reduction in myocardial β-adrenoceptor density in experimental animals with diabetes 2, 4, 5, 6, 7, the radioligand binding study using [3H]CGP 12177 revealed that the density of β-adrenoceptors was reduced by 50% in ventricular myocardium from rats with 4- to 6-week streptozotocin-induced diabetes. In the present study, we found that this animal model exhibited a significant decrease in the level of myocardial β1

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