ATP敏感性钾通道的效应器可抑制生长抑素和生长激素释放因子对生长激素分泌的调节作用。

Effectors of ATP-sensitive K+ channels inhibit the regulatory effects of somatostatin and GH-releasing factor on growth hormone secretion.

作者信息

De Weille J R, Fosset M, Epelbaum J, Lazdunski M

机构信息

Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.

出版信息

Biochem Biophys Res Commun. 1992 Sep 16;187(2):1007-14. doi: 10.1016/0006-291x(92)91297-4.

DOI:10.1016/0006-291x(92)91297-4

PMID:1356334

Abstract

Somatostatin inhibition of growth hormone (GH) secretion from adenohypophysis cells in culture was antagonized by the antidiabetic sulfonylurea glipizide (K0.5 = 10 +/- 5 nM). Although all cells that hyperpolarize with somatostatin have ATP-sensitive K+ channels, the antagonistic actions of the hormone and of the antidiabetic drug are due to effects on different types of K+ channels. Diazoxide, an opener of ATP-sensitive K+ channels, abolished the increase of intracellular Ca2+ provoked by growth hormone releasing factor (GRF) and induced inhibition of GRF stimulated GH secretion (K0.5 = 138 microM). This inhibition by diazoxide was largely suppressed by glipizide which blocked the ATP-sensitive K+ channels opened by diazoxide. In summary, hormonal activation of GH secretion is inhibited by openers of ATP-sensitive K+ channels, while hormonal inhibition of GH secretion is suppressed by blockers of ATP-sensitive K+ channels.

摘要

生长抑素对培养的腺垂体细胞生长激素（GH）分泌的抑制作用可被抗糖尿病磺脲类药物格列吡嗪拮抗（半数抑制浓度[K0.5]=10±5 nM）。尽管所有对生长抑素发生超极化的细胞都有ATP敏感性钾通道，但该激素和抗糖尿病药物的拮抗作用是由于对不同类型钾通道的影响。二氮嗪是一种ATP敏感性钾通道开放剂，它消除了生长激素释放因子（GRF）引起的细胞内Ca2+增加，并诱导对GRF刺激的GH分泌的抑制（K0.5=138 μM）。二氮嗪的这种抑制作用在很大程度上被格列吡嗪抑制，后者阻断了由二氮嗪开放的ATP敏感性钾通道。总之，ATP敏感性钾通道开放剂抑制GH分泌的激素激活，而ATP敏感性钾通道阻滞剂抑制GH分泌的激素抑制。