Date of Award

1983

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmaceutical Sciences

First Advisor

Robert L. Rodgers

Abstract

Diabetes mellitus is associated with a reduced responsiveness to catecholamines. The reduced responsiveness may be attributable to a reduction in beta-adrenoceptor sensitivity to catecholamines. Radioligand binding studies demonstrate that chemically-induced diabetes reduces beta-adrenoceptor number without altering betaadrenoceptor drug binding affinities. The present study re-examines the effect of chronic (10 weeks) streptozotocin-induced diabetes in the rat on beta-adrenoceptor drug binding affinity, using pharmacological techniques, to test the results of the binding studies. The study employed two different methods: partial irreversible receptor blockade and the use of a partial agonist, to determine betaadrenoceptor agonist binding affinity and the method of competitive antagonism to determine beta-adrenoceptor antagonist binding affinity. Diabetes produced no significant differences in the dissociation constants (l/affinity) for isoproterenol or for metaproterenol and no significant differences in the pAz values for timolol maleate which correlates to antagonist binding affinity. Therefore, the study confirms the results of radioligand binding studies by using intact tissue that diabetes does not alter beta-adrenoceptor drug binding affinity in cardiac tissue.

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