SUBUNIT COMPOSITION OF G(O) PROTEINS FUNCTIONALLY COUPLING GALANIN RECEPTORS TO VOLTAGE-GATED CALCIUM CHANNELS

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 GH(3). Injection of antisense oligonucleotides directed against alpha(o1), 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 GH(3) and in RINm5F cells couple mainly to the G(o) protein consisting of alpha(o1)beta(2) gamma(2), to inhibit Ca2+ channels and use alpha(o1)beta(3) gamma(4) less efficiently. The latter G protein composition was previously shown to be used by muscarinic M(4) receptors to inhibit Ca2+ channels.