title: Involvement of G-protein alpha il subunits in activation of G-protein gated inward rectifying K+ channels (GIRK1) by human NPY1 receptors.
abstract: 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 D2(short) dopamine receptors, and GIRK1 a cloned rat brain K+ channel. These receptors were also co-injected with G-protein alpha i1, 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; EC50 = 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 D2 receptors to this channel was not.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex. U.K.
authors.forename: N A
authors.initials: NA
authors.lastname: Brown
authors.forename: G
authors.initials: G
authors.lastname: McAllister
authors.forename: D
authors.initials: D
authors.lastname: Weinberg
authors.forename: G
authors.initials: G
authors.lastname: Milligan
authors.forename: G R
authors.initials: GR
authors.lastname: Seabrook
mesh_terms: D000818:Animals; D004247:DNA / Q000096:biosynthesis; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D014981:Xenopus
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D015221:Potassium Channels; D017448:Receptors, Dopamine D2; D017476:Receptors, Neuropeptide Y; D019257:Quinpirole; D013469:Sulpiride; D004247:DNA; D019204:GTP-Binding Proteins