Effect of reserpine pretreatment on mechanical responsiveness and [125I]Iodohydroxybenzylpindolol binding sites in the guinea-pig right atrium.
The inotropic and chronotropic responses of the guinea-pig right atrium to several pharmacologic agents were measured after acute (0.1 mg/kg/day x 1) and chronic (0.1 mg/kg/day x 7) reserpine administration. A small increase in the sensitivity of the pacemaker to isoproterenol occurred after acute 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 calcium, 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, calcium 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 [125]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 of protein). The agonist potency series for the inhibition of I-HYP binding was identical to the series for mediating mechanical responses. Taken collectively this information suggests that the high affinity I-HYP binding site in the guinea-pig right atrium represents the beta adrenergic receptor. As determined by Scatchard analyses, neither acute (1-day) nor chronic (7-day) low-dose (0.1 mg/kg/day) reserpine administration altered the number or affinity of I-HYP binding sites. It is concluded that changes in beta receptor characteristics are not responsible for reserpine-induced supersensitivity in this tissue.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006325:Heart Atria / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D010862:Pilocarpine; D000628:Aminophylline; C011878:iodohydroxybenzylpindolol; D006632:Histamine; D012110:Reserpine; D010869:Pindolol; D007545:Isoproterenol; D002118:Calcium