SER‐7b, a constitutively active Gαs coupled 5‐HT7‐like receptor expressed in the Caenorhabditis elegans M4 pharyngeal motorneuron

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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‐HT7 receptor family. Membranes from COS‐7 cells expressing SER‐7b exhibit saturable [3H]‐LSD binding (Kd = 45 nm) 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 (pEC50 = 7.5 ± 0.5). Mammalian 5‐HT7 receptor inverse agonists reduce constitutive activity, with methiothepin the most potent (pIC50 = 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 Gαs 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.