Mechanisms of cardiac supersensitivity to sympathomimetic amines

Broadley, K. J. and Williams, R. G. and Hawthorn, M. H. and Grassby, Paul (1984) Mechanisms of cardiac supersensitivity to sympathomimetic amines. Methods and Findings in Experimental and Clinical Pharmacology, 6 (4). pp. 179-186. ISSN 0379-0355

Full content URL: http://www.ncbi.nlm.nih.gov/pubmed/6087048

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Item Type:Article
Item Status:Live Archive

Abstract

Supersensitivity of the beta-adrenoceptor-mediated positive inotropic and chronotropic responses of the heart to sympathomimetic amines is considered. The various types of supersensitivity of both pre- and post-synaptic origins are described and the possible mechanisms involved are discussed. Emphasis is given to the supersensitivity that arises from depletion of sympathetic catecholamine stores by reserpine and 6-hydroxydopamine. Results are presented which indicate that in both cases the supersensitivity develops slowly, is specific for the beta-adrenoceptor and is not associated with an increase in affinity of agonists for the receptor. Radioligand binding data is presented to show that there is no increase in the total number of beta-adrenoceptor binding sites in membrane fractions from ventricular homogenates of animals receiving reserpine. A review of the literature on binding studies indicates two opposing views with respect to the effects of reserpine on beta-adrenoceptor binding sites, one showing no change and the other showing an increase in total binding sites. Limited studies in the literature show that 6-hydroxydopamine may increase the number of sites. Binding data therefore remains inconclusive and must be interpreted with caution. The relationship between the development of depletion-induced supersensitivity and the innervation of the tissue and its receptor type is discussed.

Keywords:Supersensitivity, Cardiac
Subjects:B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
Divisions:College of Science > School of Pharmacy
ID Code:8909
Deposited On:17 Apr 2013 19:24

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