Liggett S B, Marker J C, Shah S D, Roper C L, Cryer P E
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
J Clin Invest. 1988 Jul;82(1):48-56. doi: 10.1172/JCI113600.
To examine putative relationships between adrenergic receptors on accessible circulating cells and relatively inaccessible extravascular catecholamine target tissues, we measured mononuclear leukocyte (MNL) and lung beta-adrenergic receptors and platelet and lung alpha-adrenergic receptors in tissues obtained from 15 patients undergoing pulmonary resection. Plasma catecholamine concentrations were measured concurrently to explore potential regulatory relationships between the activity of the sympathochromaffin system and both intravascular and extravascular adrenergic receptors. MNL and lung membrane beta-adrenergic receptor densities were correlated highly (r = 0.845, P less than 0.001). Platelet alpha 2-adrenergic receptor and lung alpha 1-adrenergic receptor densities were not. Lung alpha 1-adrenergic receptor densities were positively related to plasma norepinephrine (r = 0.840, P less than 0.01) and epinephrine (r = 0.860, P less than 0.01) concentrations; in contrast, lung beta-adrenergic receptor densities were not positively related to plasma catecholamine concentrations (they tended to be inversely related to plasma norepinephrine and epinephrine [r = -0.698, P less than 0.05] levels). This apparent reciprocal regulation of alpha- and beta-adrenergic receptors by the sympathochromaffin system was only demonstrable with adrenergic receptor measurements in the extravascular catecholamine target tissue. Neither MNL beta-adrenergic receptor nor platelet alpha-adrenergic receptor densities were correlated with plasma catecholamine levels. Thus, although measurements of beta-adrenergic receptors on circulating mononuclear leukocytes can be used as indices of extravascular target tissue beta-adrenergic receptor densities (at least in lung and heart), it would appear that extravascular tissues should be used to study adrenergic receptor regulation by endogenous catecholamines in humans. These data provide further support for the concept of up regulation, as well as down regulation, of some adrenergic receptor populations during short-term activation of the sympathochromaffin system in humans.
为了研究可及的循环细胞上的肾上腺素能受体与相对不可及的血管外儿茶酚胺靶组织之间的假定关系,我们测量了15例接受肺切除术患者的组织中的单核白细胞(MNL)和肺β-肾上腺素能受体以及血小板和肺α-肾上腺素能受体。同时测量血浆儿茶酚胺浓度,以探索交感嗜铬系统活性与血管内和血管外肾上腺素能受体之间的潜在调节关系。MNL和肺膜β-肾上腺素能受体密度高度相关(r = 0.845,P < 0.001)。血小板α2-肾上腺素能受体和肺α1-肾上腺素能受体密度则不然。肺α1-肾上腺素能受体密度与血浆去甲肾上腺素(r = 0.840,P < 0.01)和肾上腺素(r = 0.860,P < 0.01)浓度呈正相关;相反,肺β-肾上腺素能受体密度与血浆儿茶酚胺浓度无正相关(它们倾向于与血浆去甲肾上腺素和肾上腺素呈负相关[r = -0.698,P < 0.05])。交感嗜铬系统对α-和β-肾上腺素能受体的这种明显的相互调节仅在血管外儿茶酚胺靶组织中的肾上腺素能受体测量中得到证实。MNLβ-肾上腺素能受体和血小板α-肾上腺素能受体密度均与血浆儿茶酚胺水平无关。因此,尽管循环单核白细胞上的β-肾上腺素能受体测量可作为血管外靶组织β-肾上腺素能受体密度的指标(至少在肺和心脏中),但似乎应该使用血管外组织来研究人类内源性儿茶酚胺对肾上腺素能受体的调节。这些数据为人类交感嗜铬系统短期激活期间某些肾上腺素能受体群体的上调以及下调概念提供了进一步支持。