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 ρ₁ and ρ₂ were detected in STC-1 cells by reverse transcription polymerase chain reaction (RT-PCR). Applying anti-ρ-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.