INVOLVEMENT OF G-PROTEIN ALPHA-I1 SUBUNITS IN ACTIVATION OF G-PROTEIN GATED INWARD RECTIFYING K+ CHANNELS (GIRK1) BY HUMAN NPY1 RECEPTORS

This study investigated the type of G-protein alpha: subunit(s) that human neuropeptide Y (NPY)(1) receptors preferentially utilize when activating G-protein gated K+ currents. Two electrode voltage-clamp recordings were made from Xenopus oocytes that had been injected with cDNAs encoding either human NPY1 or D-2(short) dopamine receptors, and GIRK1 a cloned rat brain K+ channel. These receptors were also co-injected with G-protein alpha il, alpha i2, alpha i3 and alpha o1 subunits to determine which subunit(s) modulate the efficiency of signal transduction. In NPY1 receptor injected cells neuropeptide Y (100 nM) caused a 53 +/- 10 nA inward current (n=14; EC(50)=3 nM) and this effect was blocked by pertussis toxin (500 ng ml(-1) 24 h). Activation of GIRK1 currents by neuropeptide Y was selectively potentiated by alpha i1 subunit cDNA whereas coupling dopamine of D-2 receptors to this channel was not.