EFFECT OF RESERPINE PRETREATMENT ON MECHANICAL RESPONSIVENESS AND [I-125]IODOHYDROXYBENZYLPINDOLOL BINDING-SITES IN THE GUINEA-PIG RIGHT ATRIUM

  • 1 January 1982
    • journal article
    • research article
    • Vol. 223  (2) , 332-341
Abstract
The inotropic and chronotropic responses of the guinea pig right atrium to several pharmacologic agents were measured after acute (0.1 mg/kg per day .times. 1) and chronic (0.1 mg/kg per day .times. 7) reserpine administration. A small increase in the sensitivity of the pacemaker to isoproterenol occurred after reserpine treatment which was followed by a much greater change in sensitivity to the .beta.-agonist when pretreatment was extended for 7 days. Chronotropic responsiveness to Ca, histamine and pilocarpine was not altered by reserpine pretreatment. The acute administration of reserpine resulted in a slight inotropic supersensitivity of paced right atria to isoproterenol, Ca and histamine. Pretreatment for 7 days produced an additional increase in inotropic sensitivity to isoproterenol but did not affect contractile responses to the other agents. The catecholamine-specific nature of the supersensitivity induced by chronic reserpine treatment suggested that a change in the number and/or affinity of .beta.-adrenergic receptors was involved. The radiolabeled .beta.-adrenoceptor antagonist [125I]iodohydroxybenzylpindolol (I-HYP) was used to test this hypothesis. Preliminary experiments revealed the presence of a single class of noninteracting (nH = 0.99), high-affinity (Kd = 100 pM) binding sites which exhibited stereospecificity and saturability (47.2 fmol/mg protein). The agonist potency series for the inhibition of I-HYP binding was identical to the series for mediating mechanical responses. The high affinity I-HYP binding site in the guinea pig right atrium apparently represents the .beta.-adrenergic receptor. As determined by Scatchard analyses, neither acute (1-day) nor chronic (7-day) low-dose (0.1 mg/kg per day) reserpine administration altered the number or affinity of I-HYP binding sites. Changes in .beta.-receptor characteristics are not responsible for reserpine-induced supersensitivity in this tissue.