Characterization of two distinct 5-HT receptors coupled to adenylate cyclase activation and ion current generation in NCB-20 cells.
The level of cyclic AMP in NCB-20 cells was increased by serotonin (5-HT), 5-methoxytryptamine and 2-methyl-5-HT with EC50 of 0.5 +/- 0.1, 1.0 +/- 0.1, 10 +/- 0.1 microM, respectively. The 5-HT-mediated increase of cyclic AMP content was completely blocked by metergoline but unaffected by 5-HT3 antagonists, ICS 205-930, MDL 72222, quipazine and 5-HT2 antagonist, ketanserin. Putative 5-HT1A agonists (8-OH-DPAT, ipsapirone, and buspirone) and 5-HT1B agonists (TFMPP and m-CPP) affected neither basal nor forskolin-dependent cyclic AMP accumulation. Receptor binding studies suggest that NCB-20 cells are devoid of 5-HT1A and 5-HT1B receptor sites. Application of 5-HT onto NCB-20 cells resulted in membrane depolarization by an evoked inward current which displayed rapid desensitization. 5-HT-mediated current had a reversal potential around 0 mV and was potently and reversibly inhibited by ICS 205-930. Our data suggest that in NCB-20 cells the 5-HT3 receptor is involved in the generation of inward currents, while the 5-HT receptor coupled to adenylate cyclase does not seem to correspond to any of the known receptor subtypes.
Cossery
J M
JM
Laboratory of Preclinical Pharmacology, St. Elizabeths Hospital, Washington, DC 20032.
Mienville
J M
JM
Sheehy
P A
PA
Mellow
A M
AM
Chuang
D M
DM
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000378:metabolism* / Q000502:physiology
D007473:Ion Channels; D011985:Receptors, Serotonin; D005576:Colforsin; D012701:Serotonin; D008735:5-Methoxytryptamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases