Pertussis toxin-insensitive G protein mediates substance P-induced inhibition of potassium channels in brain neurons.
Substance P excites neurons by suppressing inward rectification channels. We have investigated whether the substance P receptor interacts with the inward rectification channels through a guanine nucleotide-binding protein (G protein) by using dissociated cultured neurons from the nucleus basalis of newborn rats. During intracellular application of guanosine 5'-[gamma-thio]triphosphate and 5'-guanylyl imidodiphosphate, hydrolysis-resistant GTP analogues that irreversibly stimulate G proteins, substance P application almost irreversibly suppressed the inward rectification channels. Pretreatment with pertussis toxin did not significantly influence substance P action. Intracellular application of cAMP and 3-isobutyl-1-methylxanthine or of 9-(tetrahydro-2-furyl)adenine (SQ 22,536), an inhibitor of adenylate cyclase, did not alter the substance P-induced response. We conclude that the inhibition of inward rectification channels by substance P is mediated through a G protein. However, the effect is not mediated through adenylate cyclase or the cAMP system. This G protein, which is insensitive to pertussis toxin, could be an unidentified G protein.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D007473:Ion Channels; D010566:Virulence Factors, Bordetella; C017759:9-(tetrahydro-2-furyl)-adenine; D013373:Substance P; D013004:Somatostatin; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000225:Adenine; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine