Kalkbrenner F, Degtiar V E, Schenker M, Brendel S, Zobel A, Heschler J, Wittig B, Schultz G
Institut für Pharmakologie der Freien Universität Berlin, Germany.
EMBO J. 1995 Oct 2;14(19):4728-37. doi: 10.1002/j.1460-2075.1995.tb00154.x.
The neuropeptide galanin is widely expressed in the central nervous system and other tissues and induces different cellular reactions, e.g. hormone release from pituitary and inhibition of insulin release from pancreatic B cells. By microinjection of antisense oligonucleotides we studied the question as to which G proteins mediate the galanin-induced inhibition of voltage-gated Ca2+ channels in the rat pancreatic B-cell line RINm5F and in the rat pituitary cell line GH3. Injection of antisense oligonucleotides directed against alpha 01, beta 2, beta 3, gamma 2 and gamma 4 G protein subunits reduced the inhibition of Ca2+ channel current which was induced by galanin, whereas no change was seen after injection of cells with antisense oligonucleotides directed against alpha i, alpha q, alpha 11, alpha 14, alpha 15, beta 1, beta 4, gamma 1, gamma 3, gamma 5, or gamma 7 G protein subunits or with sense control oligonucleotides. In view of these data and of previous results, we conclude that the galanin receptors in GH3 and in RINm5F cells couple mainly to the G(0) protein consisting of alpha 01 beta 2 gamma 2 to inhibit Ca2+ channels and use alpha 01beta 3 gamma 4 less efficiently. The latter G protein composition was previously shown to be used by muscarinic M4 receptors to inhibit Ca2+ channels.
神经肽甘丙肽在中枢神经系统和其他组织中广泛表达，并能诱导不同的细胞反应，如垂体激素释放以及胰腺β细胞胰岛素释放的抑制。通过显微注射反义寡核苷酸，我们研究了在大鼠胰腺β细胞系RINm5F和大鼠垂体细胞系GH3中，哪些G蛋白介导甘丙肽诱导的电压门控Ca2+通道抑制作用的问题。注射针对α01、β2、β3、γ2和γ4 G蛋白亚基的反义寡核苷酸可降低甘丙肽诱导的Ca2+通道电流抑制作用，而注射针对αi、αq、α11、α14、α15、β1、β4、γ1、γ3、γ5或γ7 G蛋白亚基的反义寡核苷酸或正义对照寡核苷酸后未见变化。鉴于这些数据和先前的结果，我们得出结论，GH3和RINm5F细胞中的甘丙肽受体主要与由α01β2γ2组成的G(0)蛋白偶联以抑制Ca2+通道，而对α01β3γ4的利用效率较低。先前已证明后一种G蛋白组成被毒蕈碱M4受体用于抑制Ca2+通道。
