title: Role of two different guanine nucleotide-binding proteins in the antagonistic modulation of the S-type K+ channel by cAMP and arachidonic acid metabolites in Aplysia sensory neurons.
abstract: The role of guanine nucleotide-binding proteins (G proteins) in the cAMP-dependent action of serotonin (5-HT) and the antagonistic action of the neuropeptide Phe-Met-Arg-Phe-NH2 (FMRF-amide), mediated by the lipoxygenase metabolites of arachidonic acid, was investigated in Aplysia sensory neurons. Intracellular injection of guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]) mimics the hyperpolarizing action of FMRF-amide due to activation of the S K+ current and alters the transient response to FMRF-amide into an irreversible (or only partially reversible) response. At higher concentrations, GTP[gamma-S] occludes the response to FMRF-amide. Injection of activated pertussis toxin inhibits the response to FMRF-amide but not to 5-HT. Injection of guanosine 5'-[beta-thio]diphosphate inhibits the response to FMRF-amide by approximately equal to 50% and completely blocks the response to 5-HT. Three lines of evidence suggest that the FMRF-amide-activated G protein is involved at an early stage of the arachidonic acid cascade, prior to the release of arachidonate. (i) Pertussis toxin injection blocks the hyperpolarizing response to FMRF-amide but not to exogenously applied arachidonic acid. (ii) Two blockers of the arachidonic acid cascade inhibit the hyperpolarizing responses to both FMRF-amide and GTP[gamma-S] (and unmask a 5-HT-like depolarizing response to the nucleotide). (iii) Concentrations of GTP[gamma-S] that alter the kinetics of the FMRF-amide response have no effect on the hyperpolarizing response to arachidonic acid. We conclude that a pertussis toxin-sensitive G protein most likely acts to couple the FMRF-amide receptor to phospholipase activation and arachidonic acid release, whereas a pertussis toxin-insensitive G protein couples the 5-HT receptor to adenylate cyclase.
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032.
authors.forename: A
authors.initials: A
authors.lastname: Volterra
authors.forename: S A
authors.initials: SA
authors.lastname: Siegelbaum
mesh_terms: D000818:Animals; D001048:Aplysia; D001095:Arachidonic Acids / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D019835:FMRFamide; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D009479:Neuropeptides; D015221:Potassium Channels; D013873:Thionucleotides; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019835:FMRFamide; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins