title: SER-7b, a constitutively active Galphas coupled 5-HT7-like receptor expressed in the Caenorhabditis elegans M4 pharyngeal motorneuron.
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 Galphas 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.
authors.affiliation: Department of Biological Sciences, University of Toledo, Ohio, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hobson
authors.forename: Jinming
authors.initials: J
authors.lastname: Geng
authors.forename: Anjali D
authors.initials: AD
authors.lastname: Gray
authors.forename: Richard W
authors.initials: RW
authors.lastname: Komuniecki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D008719:Methiothepin / Q000493:pharmacokinetics; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism*; D010614:Pharynx / Q000378:metabolism*; D010802:Phylogeny; D011985:Receptors, Serotonin / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000493:pharmacokinetics; D012702:Serotonin Antagonists / Q000493:pharmacokinetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D011985:Receptors, Serotonin; C478614:SER-7b protein, C elegans; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor; D012701:Serotonin; D008719:Methiothepin; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins