Biphasic Adrenergic Modulation of β-Adrenergic Receptors in Man: AGONIST-INDUCED EARLY INCREMENT AND LATE DECREMENT IN β-ADRENERGIC RECEPTOR NUMBER
Biphasic Adrenergic Modulation of β-Adrenergic Receptors in Man: AGONIST-INDUCED EARLY INCREMENT AND LATE DECREMENT IN β-ADRENERGIC RECEPTOR NUMBER
复制标题
人体β-肾上腺素能受体的双相肾上腺素调节：激动剂引起的β-肾上腺素能受体数量的早期增加和晚期减少
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发表时间：
1980
期刊：
影响因子：
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通讯作者：
P. Cryer
中科院分区：
文献类型：
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作者：
J. F. Tohmeh;P. Cryer
：在向正常人受试者输注肾上腺素能激动剂期间，采用（-）[（3）H]-二氢阿普洛尔结合研究评估单核白细胞制剂中的β-肾上腺素能受体。在向7名受试者输注异丙肾上腺素期间，平均（+/-SE）（-）[（3）H]二氢阿普洛尔结合从25+/-3 fmol/mg蛋白增加至47+/-8 fmol/mg蛋白在0.5 h和1 h时分别为40+/-3 fmol/mg蛋白（P <0.01）和12+/-1 fmol/mg蛋白（P < 0.01）。在3名受试者输注肾上腺素期间，在0.5-1小时，平均（-）[（3）H]二氢阿普洛尔结合从32+/-3增加到63+/-3 fmol/mg蛋白（P < 0.01）。通过Scatchard图分析，这些变化可归因于可用结合位点数量的变化，而不是结合亲和力的变化。观察到的（-）[（3）H]二氢阿普洛尔结合位点数量的变化不受总单核细胞计数或T淋巴细胞、B淋巴细胞和单核细胞分布变化的影响。因此，我们得出结论，肾上腺素能激动剂以双相方式调节循环单核细胞上可用的β-肾上腺素能受体的数量，在人类中具有早期增加和晚期减少。在激动剂输注0.5-1小时后，响应于异丙肾上腺素的“脉冲”输注的脉搏率的增加显著更大，这一发现表明观察到的早期激动剂-循环细胞上β-肾上腺素能受体数量的诱导增加被血管外β-肾上腺素能受体敏感性的增加所抵消。
: beta-Adrenergic receptors in mononuclear leukocyte preparations were assessed with (-)[(3)H]-dihydroalprenolol binding studies during the infusion of adrenergic agonists into normal human subjects. During the infusion of isoproterenol into seven subjects, mean (+/-SE) (-)[(3)H]dihydroalprenolol binding increased from 25+/-3 fmol/mg protein to 47+/-8 fmol/mg protein (P < 0.02) at 0.5 h and 40+/-3 fmol/mg protein (P < 0.01) at 1 h and decreased to 12+/-1 fmol/mg protein (P < 0.01) at 4-6 h. During the infusion of epinephrine into three subjects, mean (-)[(3)H]dihydroalprenolol binding increased from 32+/-3 to 63+/-3 fmol/mg protein (P < 0.01) at 0.5-1 h. By Scatchard plot analysis, these changes were attributable to changes in the number of available binding sites rather than changes in binding affinity. The observed changes in the number of (-)[(3)H]dihydroalprenolol binding sites were not paralleled by changes in total mononuclear cell counts or in T lymphocyte, B lymphocyte, and monocyte distributions. Thus, we conclude that adrenergic agonists modulate the number of available beta-adrenergic receptors on circulating mononuclear cells in a biphasic manner, with an early increment and a late decrement, in man. Further, the finding that the increase in pulse rate in response to a "pulse" infusion of isoproterenol was significantly greater after 0.5-1 h of agonist infusion suggests that the observed early agonist-induced increment in beta-adrenergic receptor number on circulating cells is paralleled by increments in extra-vascular beta-adrenergic receptor sensitivity.