Renal alpha 2-adrenoceptors and the adenylate cyclase-cAMP system: biochemical and physiological interactions.
Renal alpha 2-adrenoceptors and the adenylate cyclase-cAMP system: biochemical and physiological interactions.
复制标题
肾α2-肾上腺素受体和腺苷酸环化酶-cAMP 系统：生化和生理相互作用。
DOI：
10.1152/ajprenal.1987.252.2.f199
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Jeffries,WB
中科院分区：
文献类型：
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作者：
Pettinger,WA;Umemura,S;Smyth,DD;Jeffries,WB
十年前，α2-肾上腺素受体首次在药理学上被描述。三年内，它们抑制腺苷酸环化酶的能力已在许多组织中得到证实。 1981 年，甚至在其激活对肾脏产生的任何生理效应为人所知之前，它们就在肾脏中得到了生化证明。它们在肾膜中的数量上超过α1-肾上腺素受体，并且它们的密度在大鼠高血压的遗传形式中增加。 α1-肾上腺素受体通常介导交感神经元释放的去甲肾上腺素的血管收缩以及钠和水的保留作用。必须输注去甲肾上腺素或肾上腺素才能激活α2-肾上腺素受体，这表明肾脏α2-肾上腺素受体是交界外的，而α1-肾上腺素受体是交界后的。当α1-肾上腺素受体长期受阻时，肾脏α2-肾上腺素受体密度增加，并且它们位于连接后部位，这是α1-肾上腺素受体的专有区域。显微解剖研究的结果已证实，α2-肾上腺素受体存在于肾单位的大多数节段上，并且它们的激活可以抑制大多数肾激素诱导的腺苷 3,'5'-环单磷酸 (cAMP) 积累。然而，α2-肾上腺素受体激活未能抑制某些激素诱导的某些管状节段中 cAMP 的积累，这表明腺苷酸环化酶调节的区室化是激素功能特异性的。鉴于α2-肾上腺素受体刺激对肾单位几个离散区域中激素激活的cAMP积累的有效抑制作用，我们认为α2-肾上腺素受体在肾功能中发挥重要的调节作用。迄今为止，α2-肾上腺素受体激活已被证明可以逆转加压素诱导的钠和水潴留，以及花生四烯酸和呋塞米诱导的离体灌注肾中的 cAMP、钠和水排泄。因此，在这些研究中，效果在质量和数量上取决于所输注的激素，因此具有激素功能特异性。甲状旁腺降钙素的α2-肾上腺素受体激活的生理作用以及甲状旁腺激素诱导的作用尚未研究。 α2-肾上腺素受体激活可以抑制某些模型系统中的肾素释放，并可以激活近曲小管中的钠-氢逆向转运蛋白系统。这些作用的生理作用尚不清楚。
alpha 2-Adrenoceptors were first described pharmacologically ten years ago. Within three years their capacity to inhibit adenylate cyclase had been demonstrated in many tissues. They were demonstrated biochemically in the kidneys in 1981 even before any renal physiological effects of their activation were known. They predominate numerically over alpha 1-adrenoceptors in renal membranes and their density is increased in genetic forms of rat hypertension. alpha 1-Adrenoceptors normally mediate the vasoconstriction and sodium- and water-retaining effects of sympathetic neuronally released norepinephrine. Norepinephrine or epinephrine must be infused to activate alpha 2-adrenoceptors, suggesting that renal alpha 2-adrenoceptors are extrajunctional, whereas alpha 1-adrenoceptors are postjunctional. When alpha 1-adrenoceptors are chronically blocked, renal alpha 2-adrenoceptor density increases and they assume a location at postjunctional sites, the otherwise exclusive domain of alpha 1-adrenoceptors. Results from microdissection studies have established that alpha 2-adrenoceptors are present on most segments of the nephron and that their activation can suppress adenosine 3,'5'-cyclic monophosphate (cAMP) accumulation induced by most renal hormones. However, failure of alpha 2-adrenoceptor activation to suppress cAMP accumulation in some tubular segments induced by certain hormones suggests compartmentalization of adenylate cyclase regulation that is hormone-function specific. In view of the potent inhibitory effects of alpha 2-adrenoceptor stimulation on hormone activated cAMP accumulation in several discrete areas of the nephron, we suggest that alpha 2-adrenoceptors fulfill important regulatory role(s) in renal function. To date, alpha 2-adrenoceptor activation has been shown to reverse vasopressin-induced sodium and water retention, and arachidonic acid- and furosemide-induced cAMP, sodium, and water excretion in the isolated perfused kidney. Thus the effects are qualitatively and quantitatively dependent in these studies on the hormone being infused and are therefore hormone-function specific. Physiological effects of alpha 2-adrenoceptor activation of thyrocalcitonin and on parathyroid hormone-induced effects have not been studied. alpha 2-Adrenoceptor activation can inhibit renin release in some model systems and can activate a sodium-hydrogen antiporter system in proximal tubules. The physiological roles of these actions are unknown.