Reid S D, Perry S F
Department of Biology, University of Ottawa, Ontario, Canada.
J Exp Biol. 1991 Jul;158:217-40. doi: 10.1242/jeb.158.1.217.
We have investigated the influence of cortisol on the beta-adrenoreceptor population of rainbow trout [Oncorhynchus mykiss (Walbaum)] erythrocytes and determined what impact it has on the adrenergic responsiveness of erythrocytes in vitro to exogenous catecholamines. To do so, the erythrocyte beta-adrenoreceptors were characterized in fish with chronically elevated plasma cortisol levels (118 +/- 5.9 ng ml-1, greater than 10 days) and compared with shams, using radioreceptor assay techniques. The number of 'internalized', low-affinity receptors was increased when cortisol levels were raised, but the number of high-affinity, 'surface' receptors was not altered. The physiological significance of this response was ascertained by assessing the in vitro sensitivity (or responsiveness) of erythrocytes to adrenaline and noradrenaline (10-1000 nmol l-1) under normoxic (PO2 = 16.13 +/- 0.55 kPa, PCO2 = 0.41 +/- 0.01 kPa) or hypoxic (PO2 = 4.13 +/- 0.15 kPa, PCO2 = 0.43 +/- 0.01 kPa) conditions. Erythrocyte sensitivity to catecholamines, as determined by changes in both whole-blood pH (delta pHe) and intracellular cyclic AMP content, was greater in hypoxic than in normoxic blood. Although cortisol further enhanced the responsiveness of erythrocytes to catecholamines, this amplification in sensitivity was observed only during hypoxia. When the radioreceptor assay was conducted using erythrocytes from the catecholamine sensitivity experiments, results were consistent with initial receptor density data. An increase in surface receptor density was associated with hypoxia in vitro. This hypoxia-specific increase in surface beta-adrenoreceptors was significantly enhanced in the cortisol-treated erythrocytes, showing that cortisol had a significant impact on erythrocyte beta-adrenoreceptor dynamics in addition to the direct influence of hypoxia. This study has shown (1) that, by itself, in vitro hypoxia simultaneously initiates the movement of internal receptors to the cell surface, where they become physiologically active, and the replenishment of the internal receptor pool, (2) that cortisol increases receptor availability by increasing the internal pool of low-affinity receptors in the absence of any stimulus for receptor mobilization, and (3) that the sensitivity of erythrocytes to catecholamines is directly proportional to the number of high-affinity receptors present at the erythrocyte surface. Thus, we suggest that, under conditions of chronic stress, cortisol may pre-adapt the erythrocytes to receive additional physiological inputs that can ultimately enhance respiratory performance beyond that which would be possible in the absence of chronically elevated levels of cortisol.
我们研究了皮质醇对虹鳟鱼[Oncorhynchus mykiss (Walbaum)]红细胞β-肾上腺素能受体群体的影响，并确定了其对体外红细胞对外源性儿茶酚胺的肾上腺素能反应性的影响。为此，我们采用放射受体分析技术，对血浆皮质醇水平长期升高（118±5.9 ng/ml，超过10天）的鱼的红细胞β-肾上腺素能受体进行了表征，并与假手术组进行了比较。当皮质醇水平升高时，“内化”的低亲和力受体数量增加，但高亲和力的“表面”受体数量未改变。通过评估常氧（PO2 = 16.13±0.55 kPa，PCO2 = 0.41±0.01 kPa）或低氧（PO2 = 4.13±0.15 kPa，PCO2 = 0.43±0.01 kPa）条件下红细胞对肾上腺素和去甲肾上腺素（10 - 1000 nmol/l）的体外敏感性（或反应性），确定了这种反应的生理意义。红细胞对儿茶酚胺的敏感性，通过全血pH值变化（δpHe）和细胞内环磷酸腺苷含量来确定，在低氧血液中比在常氧血液中更高。虽然皮质醇进一步增强了红细胞对儿茶酚胺的反应性，但这种敏感性的增强仅在低氧期间观察到。当使用来自儿茶酚胺敏感性实验的红细胞进行放射受体分析时，结果与初始受体密度数据一致。体外低氧与表面受体密度增加有关。在皮质醇处理的红细胞中这种低氧特异性表面β-肾上腺素能受体增加显著增强，表明除了低氧的直接影响外，皮质醇对红细胞β-肾上腺素能受体动力学有显著影响。这项研究表明：（1）体外低氧本身同时引发内部受体向细胞表面移动，在那里它们变得具有生理活性，以及内部受体库的补充；（2）皮质醇在没有任何受体动员刺激的情况下，通过增加低亲和力受体的内部库来增加受体可用性；（3）红细胞对儿茶酚胺的敏感性与红细胞表面存在的高亲和力受体数量成正比。因此，我们认为，在慢性应激条件下，皮质醇可能使红细胞预先适应接受额外的生理输入，最终增强呼吸性能，超过在没有长期升高的皮质醇水平时可能达到的水平。
