title: GABA(C) receptors in neuroendocrine gut cells: a new GABA-binding site in the gut.
abstract: Although GABA(C) receptors play a crucial role in the mammalian central nervous system, their functional expression in peripheral tissues has not yet been studied. Using the gut neuroendocrine tumor cell line STC-1 as a model, we provide first evidence for the functional expression of GABA(C) receptors in the gut: mRNAs of the GABA(C) receptor subunits rho1 and rho2 were detected in STC-1 cells by reverse transcription polymerase chain reaction (RT-PCR). Applying anti-rho-antibodies, specific immunostaining for GABA(C) receptors was observed. For functional characterization, the effects of GABA(C) receptor activation on [Ca2+]i and hormone secretion were studied. The selective GABA(C) receptor agonist cis-4-aminocrotonic acid (CACA) induced dose-dependent increases both of [Ca2+]i and of hormone (cholecystokinin) secretion. The stimulatory effects of CACA were antagonized by the GABA(C) receptor blockers (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and 3-aminopropyl(methyl)phosphinic acid (3-APMPA). These results demonstrate that GABA(C) receptors play an important role in neuroendocrine gastrointestinal secretion.
authors.affiliation: Medizinische Klinik I, Gastroenterologie und Infektiologie, Universitätsklinikum Benjamin Franklin, Freie Universität, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Jansen
authors.forename: M
authors.initials: M
authors.lastname: Hoepfner
authors.forename: K H
authors.initials: KH
authors.lastname: Herzig
authors.forename: E O
authors.initials: EO
authors.lastname: Riecken
authors.forename: H
authors.initials: H
authors.lastname: Scherübl
mesh_terms: D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism; D003561:Cytarabine / Q000031:analogs & derivatives / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D015870:Gene Expression; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D018358:Neuroendocrine Tumors / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018079:Receptors, GABA / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000179:Acrylates; D018756:GABA Antagonists; C087200:GABA-C receptor; D009943:Organophosphorus Compounds; D011724:Pyridazines; D012333:RNA, Messenger; D018079:Receptors, GABA; D003561:Cytarabine; C055054:N(4)-chloroacetylcytosine arabinoside; C068457:3-aminopropyl(methyl)phosphinic acid; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; C058552:3-((aminoiminomethyl)thio)-2-propenoic acid; C049853:gabazine; D002118:Calcium; D001640:Bicuculline