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猪甲状腺中α2-肾上腺素能受体的优势:生化与药理学相关性

Predominance of alpha 2-adrenoceptors in porcine thyroid: biochemical and pharmacological correlations.

作者信息

Muraki T, Nakaki T, Kato R

出版信息

Endocrinology. 1984 May;114(5):1645-51. doi: 10.1210/endo-114-5-1645.

Abstract

alpha-Adrenergic agonists such as norepinephrine and clonidine, but not methoxamine, inhibited the increase in cAMP accumulation elicited by TSH in porcine thyroid slices. The inhibitory effect of norepinephrine was abolished by yohimbine but not by prazosin. Likewise, the in vitro release of T4 from the pig thyroid slice stimulated by TSH was inhibited by norepinephrine and the inhibition was antagonized by yohimbine but not by prazosin. These results suggest that the inhibitory effect of alpha-adrenergic agonists is mediated through alpha 2-adrenoceptors. Preincubation of the thyroid slices with islet-activating protein, pertussis toxin, decreased the inhibitory effect of norepinephrine on the cAMP content, suggesting the involvement of guanine nucleotide regulatory protein (Ni) in the inhibition mediated through alpha 2-adrenoceptors. Binding studies with [3H]yohimbine and [3H]prazosin to porcine thyroid membranes revealed the specific and saturable binding of both radioligands. Scatchard analysis of the specific binding revealed a single class of binding sites for each radioligand; however, the maximum number of binding sites for [3H]yohimbine was about 10 times more than that for [3H]prazosin. In accordance with the pharmacological results, binding studies showed a predominance of alpha 2-adrenoceptors in the pig thyroid.

摘要

去甲肾上腺素和可乐定等α-肾上腺素能激动剂,但甲氧明则不能,可抑制猪甲状腺切片中促甲状腺激素(TSH)引起的环磷酸腺苷(cAMP)积累增加。育亨宾可消除去甲肾上腺素的抑制作用,而哌唑嗪则不能。同样,去甲肾上腺素可抑制TSH刺激的猪甲状腺切片中甲状腺素(T4)的体外释放,且育亨宾可拮抗这种抑制作用,而哌唑嗪则不能。这些结果表明,α-肾上腺素能激动剂的抑制作用是通过α2-肾上腺素能受体介导的。用胰岛激活蛋白、百日咳毒素对甲状腺切片进行预孵育,可降低去甲肾上腺素对cAMP含量的抑制作用,提示鸟嘌呤核苷酸调节蛋白(Ni)参与了通过α2-肾上腺素能受体介导的抑制过程。用[3H]育亨宾和[3H]哌唑嗪对猪甲状腺膜进行结合研究,发现两种放射性配体均有特异性和饱和性结合。对特异性结合进行Scatchard分析,发现每种放射性配体都有一类结合位点;然而,[3H]育亨宾的结合位点最大数量约为[3H]哌唑嗪的10倍。与药理学结果一致,结合研究表明猪甲状腺中α2-肾上腺素能受体占优势。

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