Antagonism by forskolin of the 5-HT3 receptor-mediated current in nodose ganglion neurons is independent of cyclic AMP.
The effect of forskolin on the inward current mediated by 5-HT3 receptors (5-HT current) was investigated in rat nodose ganglion neurons. Forskolin inhibited the peak amplitude of the 5-HT current and increased current desensitization in a dose-dependent manner. Dideoxyforskolin, which does not stimulate adenylate cyclase, had a similar inhibitory effect on the 5-HT current. The effect of forskolin was neither mimicked by intracellular application of exogenous cyclic AMP (0.5 to 4 mM) nor occluded by intracellular forskolin (30 microM) or protein kinase inhibitor H-7 (100 microM). Intracellular applications of forskolin, cyclic AMP or H-7 had no effect on 5-HT current. Data suggest that forskolin acted at an extracellular site on 5-HT3 receptors and this effect of forskolin was not mediated by cyclic AMP-dependent processes.
Fan
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Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*
D007473:Ion Channels; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012702:Serotonin Antagonists; D005576:Colforsin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; C047983:1,9-dideoxyforskolin