Comparison of changes in the characteristics of ?-adrenoceptors and responsiveness of human circulating lymphocytes during and after chronic administration of pindolol and propranolol

Abstract

The characteristics of the beta-adrenoceptors (3H-dihydroalprenolol binding) and the beta-adrenergic responsiveness (cyclic AMP response to isoproterenol) were studied in circulating lymphocytes from healthy volunteers before (D 0), on the 22nd day of treatment (D 22) and on the fifth day (D 30) following discontinuation of pindolol 15 mg/day or propranolol 160 mg/day. During pindolol therapy (D 22) the beta-adrenoceptor-affinity towards dihydroalprenolol was unchanged and the beta-adrenoceptor density decreased by 50%, an effect which persisted after drug administration ceased (D 30). The receptor "down-regulation" was accompanied by a parallel decrease in the maximal lymphocyte response to isoproterenol on D 22 and 30, by a shift to the right of the concentration-response curves to isoproterenol on D 22 and 30. In contrast, no significant modification in beta-adrenoceptor density or in the maximal response to isoproterenol was observed during (D 22) or after discontinuation (D 30) or propranolol therapy; the beta-adrenoceptor affinity for dihydroalprenolol and the sensitivity of the lymphocyte response to isoproterenol were markedly reduced on D 22 but not on D 30. It is concluded that the lymphocyte beta-adrenoceptor "down regulation" and the parallel beta-adrenergic desensitization induced by chronic pindolol therapy are both due to the intrinsic sympathomimetic activity of this drug.

Effects of Chronic Administration of Carteolol on .BETA.-Adrenoceptors in Spontaneously Hypertensive Rat Heart.

“…On the other hand, 0.3 mg/kg carteolol (which is nearly equipotent to 30 mg/kg propranolol) had no effect on /8 adrenoceptors in SHR heart, and 10 mg/kg carteolol decreased the number of a-adre noceptors in SHR heart without significant changes in the Kd values. Our results are in agreement with those of other investigators who suggested that the "rebound phenomena" after withdrawal would not occur following /3 adrenoceptor antagonists with ISA (8)(9)(10). In WKY, we observed a significant increase in heart rate at 10 weeks following 10 mg/kg car teolol (16-week old), suggesting that the ISA was actually acting in carteolol-treated WKY.…”

“…Several investigators found that in human lymphocytes, chronic treatment with proprano lol led to an increase in the number of /3 adrenoceptors, while chronic treatment with ,Q-adrenoceptor antagonists with intrinsic sym pathomimetic activity (ISA) did not lead to an increase (but rather led to a decrease) in the number of /3-adrenoceptors (8)(9)(10). Based on these results, they suggested that "rebound phenomena" could be prevented by the use of /3-adrenoceptor antagonists with ISA.…”

Beta receptor antagonists in the treatment of heart failure

“…These receptors do not seem to be downregulated in the hearts of patients in failure (Bristow, 1989). The nonselective beta-blocker propranolol causes upregulation of lymphocyte receptors [50][51][52], whereas the nonselective compound pindolol with ISA causes downregulation [50,52,53]. Acebutolol, a betal-selecrive ISA drug, does not induce downregulation in lymphocyte receptors [53].…”

Influence of Long‐Term Prenalterol Treatment on the Heart Rate and the β‐Adrenoceptor Binding‐Sites in Rat Myocardium

“…Perkins et al (198 1) have demonstrated that P-adrenoceptor agonists, but not antagonists, can initiate the process of desensitization. However, it was recently observed that chronic therapy with pindolol, a P-adrenoceptor antagonist with intrinsic sympathomimetic activity, induced a P-adrenoceptor desensitization in human lymphocytes (Giudicelli et al 1984). Whether prenalterol which can act as both an agonist and an antagonist behaves in the same way in this respect during long-term treatment, remains to be demonstrated.…”