SER‐7b, a constitutively active Gα s coupled 5‐HT 7 ‐like receptor expressed in the Caenorhabditis elegans M4 pharyngeal motorneuron

• Published in: Journal of neurochemistry Vol. 87; no. 1; pp. 22 - 29
• Main Authors: Hobson, Robert J., Geng, Jinming, Gray, Anjali D., Komuniecki, Richard W.
• Format: Journal Article
• Language: English
• Published: 01.10.2003
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.01967.x

Abstract Serotonin plays a key role in the regulation of pharyngeal pumping in nematodes. We have isolated a Caenorhabditis elegans cDNA (C09B7.1b, ser‐7b ) with greatest identity to the 5‐HT 7 receptor family. Membranes from COS‐7 cells expressing SER‐7b exhibit saturable [ 3 H]‐LSD binding ( K d  = 45 n m ) that is inhibited by serotonin (5‐HT) and tryptamine, but not by other physiological biogenic amines. Expression of SER‐7b in COS‐7 cells results in dramatic increase in basal cAMP levels over untransfected cells that is dependent on expression level. 5‐HT further elevates cAMP levels in a dose‐dependent manner (pEC 50  = 7.5 ± 0.5). Mammalian 5‐HT 7 receptor inverse agonists reduce constitutive activity, with methiothepin the most potent (pIC 50  = 7.8 ± 0.1). Ser‐7 ::GFP transcriptional fusions reveal that SER‐7b appears to be expressed solely in the M4 pharyngeal motorneuron after hatching. This is the first report of a Gα s coupled biogenic amine receptor in nematodes and the localization of SER‐7b in the M4 pharyngeal motorneuron suggests that SER‐7b may play a role in the regulation of pharyngeal pumping.