Snavely M D, Mahan L C, O'Connor D T, Insel P A
Endocrinology. 1983 Jul;113(1):354-61. doi: 10.1210/endo-113-1-354.
We have used an animal model of pheochromocytoma and radioligand-binding techniques to examine the effects of high levels of circulating norepinephrine and dopamine on adrenergic receptor subtypes in several peripheral tissues. New England Deaconess Hospital rats with transplanted pheochromocytomas were hypertensive and had levels of plasma norepinephrine and dopamine 50-fold greater than those of controls. The number of beta-adrenergic receptors in membranes prepared from the renal cortex and the left ventricle from these rats was decreased about 50%, but the animals had no significant decrease in the overall number of beta-adrenergic receptors in pulmonary membranes. beta-Receptor affinity was unaltered in animals with pheochromocytoma. Competition for [125I]iodocyanopindolol binding to beta-receptors by subtype-selective agents indicated a selective decrease of about 80% in the number of beta 1-adrenergic receptors in renal cortical and pulmonary membranes, without a decrease in beta 2-adrenergic receptor number. Rats with pheochromocytoma also had about a 70% decrease in the number of alpha 1-adrenergic receptors in membranes from renal cortex and lung, but no significant decrease in the number of alpha 1-adrenergic receptors in hepatic membranes and no decrease in the number of alpha 2-adrenergic receptors in renal cortical and hepatic membranes. These results indicate that rats in which pheochromocytomas are transplanted show adrenergic receptor subtype- and tissue-specific down-regulation. Although the selective down-regulation of alpha 1- and beta 1-adrenergic receptors may reflect a response to the preponderance of norepinephrine in these animals, the results indicate that different tissues and different adrenergic receptor subtypes may have varying susceptibility to down-regulation in response to increased circulating catecholamines in vivo.
我们使用嗜铬细胞瘤动物模型和放射性配体结合技术，来研究循环中高水平去甲肾上腺素和多巴胺对几种外周组织中肾上腺素能受体亚型的影响。移植了嗜铬细胞瘤的新英格兰女执事医院大鼠患有高血压，其血浆去甲肾上腺素和多巴胺水平比对照组高50倍。这些大鼠肾皮质和左心室制备的膜中β-肾上腺素能受体数量减少了约50%，但肺部膜中β-肾上腺素能受体总数无显著减少。嗜铬细胞瘤动物的β受体亲和力未改变。亚型选择性药物对[125I]碘氰吲哚洛尔与β受体结合的竞争表明，肾皮质和肺膜中β1-肾上腺素能受体数量选择性减少约80%，而β2-肾上腺素能受体数量未减少。患有嗜铬细胞瘤的大鼠肾皮质和肺膜中α1-肾上腺素能受体数量也减少了约70%，但肝膜中α1-肾上腺素能受体数量无显著减少，肾皮质和肝膜中α2-肾上腺素能受体数量也未减少。这些结果表明，移植了嗜铬细胞瘤的大鼠表现出肾上腺素能受体亚型和组织特异性下调。虽然α1-和β1-肾上腺素能受体的选择性下调可能反映了这些动物对去甲肾上腺素优势的反应，但结果表明，不同组织和不同肾上腺素能受体亚型对体内循环儿茶酚胺增加导致的下调可能具有不同的敏感性。
