The effect of streptozotocin-induced diabetes on cardiac beta-adrenoceptor subtypes in the rat.
1. The present study investigates the effect of short-term experimental diabetes of 14-days duration on the beta-adrenoceptor subtypes of the rat heart. 2 .beta-adrenoceptor-mediated functional responses to submaximal doses of isoprenaline were enhanced in Langendorff-perfused hearts from diabetic rats, manifested as greater changes in tension, heart rate and rates of tension development (+dT/dt) and decline (-dT/dt). 3. Radioligand binding data demonstrated that total cardiac beta-adrenoceptor density and affinity for [3H]-dihydroalprenolol was unchanged by diabetes, although a decrease in beta1-adrenoceptor density and increase in beta2-adrenoceptor density was observed. 4. In conclusion, hearts from 14-day streptozotocin-induced diabetic rats demonstrate a number of alterations within the beta-adrenoceptor system. However, the enhanced beta-adrenoceptor-mediated responses to isoprenaline were not caused by an overall increase in density of beta-adrenoceptors, but were accompanied by changes in the ratio of the beta-adrenoceptor subtypes.
Sellers
D J
DJ
Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
Chess-Williams
R
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D013311:Streptozocin
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D007093:Imidazoles; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D013311:Streptozocin; D004082:Dihydroalprenolol; C049763:CGP 20712A; D007545:Isoproterenol