Hedberg A, Gerber J G, Nies A S, Wolfe B B, Molinoff P B
J Pharmacol Exp Ther. 1986 Oct;239(1):117-23.
The cardiovascular supersensitivity observed after discontinuation of administration of beta adrenergic receptor antagonists may be explained by an increase in the density of beta adrenergic receptors. Thus, a change in the density of receptors has been observed in human lymphocytes after administration of propranolol (Aarons et al., 1980). The effects of pindolol, a beta adrenergic receptor antagonist with intrinsic sympathomimetic activity, were compared with those of propranolol or placebo. Pindolol (10 mg q.i.d.), propranolol (40 mg q.i.d.) or placebo were administered to 12 subjects for 8 days. The density of beta adrenergic receptors was determined by Scatchard analysis of the specific binding of [125I]iodopindolol on membranes prepared from human lymphocytes. Administration of pindolol resulted in a 30 to 50% decrease in the density of beta adrenergic receptors. This decrease was apparent within 1 day of beginning pindolol administration and it persisted for at least 8 days after discontinuation of drug administration. The reversibility of the decrease in receptors observed after pindolol administration was studied in 27 subjects given propranolol, pindolol or placebo for 4 days in a double-blind cross-over trial. Propranolol consistently induced a small increase in the density of beta adrenergic receptors. The density of receptors returned to predrug values within 2 days after discontinuation of propranolol administration. Pindolol induced a 30 to 50% decrease in the density of receptors which, as observed previously, persisted for at least 10 days after discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
停用β肾上腺素能受体拮抗剂后观察到的心血管超敏反应可能是由于β肾上腺素能受体密度增加所致。因此，在给予普萘洛尔后，已观察到人类淋巴细胞中受体密度发生变化（阿伦斯等人，1980年）。将具有内在拟交感活性的β肾上腺素能受体拮抗剂吲哚洛尔的作用与普萘洛尔或安慰剂的作用进行了比较。将吲哚洛尔（10毫克，每日4次）、普萘洛尔（40毫克，每日4次）或安慰剂给予12名受试者，持续8天。通过对[125I]碘吲哚洛尔与人淋巴细胞制备的膜上特异性结合进行Scatchard分析来测定β肾上腺素能受体的密度。给予吲哚洛尔导致β肾上腺素能受体密度降低30%至50%。这种降低在开始给予吲哚洛尔后1天内就很明显，并且在停药后至少持续8天。在一项双盲交叉试验中，对27名给予普萘洛尔、吲哚洛尔或安慰剂治疗4天的受试者研究了吲哚洛尔给药后观察到的受体密度降低的可逆性。普萘洛尔始终导致β肾上腺素能受体密度小幅增加。停用普萘洛尔给药后2天内，受体密度恢复到用药前水平。吲哚洛尔导致受体密度降低30%至50%，如先前观察到的，在停药后至少持续10天。（摘要截短于250字）
