Mechanisms of cardiac supersensitivity to sympathomimetic amines.
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.
D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009921:Metaproterenol / Q000494:pharmacology; D016627:Oxidopamine; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013566:Sympathomimetics / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors
D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D009921:Metaproterenol; D012110:Reserpine; D016627:Oxidopamine; D007545:Isoproterenol