Expression of functional GABAA receptors in cholecystokinin‐secreting gut neuroendocrine murine STC‐1 cells

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Abstract
1 Gastrointestinal neuroendocrine (NE) cells synthesize, store and secrete γ-aminobutyric acid (GABA). Recently, an autocrine-paracrine function of GABA has been proposed for secretion from NE cells. 2 To search for functional GABAA receptors in NE gut cells, we performed whole-cell and perforated-patch-clamp studies in the intestinal cholecystokinin (CCK)-secreting NE cell line STC-1. 3 Application of GABA evoked currents in STC-1 cells. These effects were mimicked by muscimol, an agonist of GABAA receptors, and blocked by picrotoxin or bicuculline, antagonists of GABAA receptors. The GABA- or muscimol-activated currents reversed near 0 mV, which under the recording conditions used was consistent with the activation of the GABAA receptor-Cl− channel complex. 4 In contrast to the effect on most neurons, GABA as well as muscimol led to a (reversible) depolarization of the membrane potential of STC-1 cells. Membrane depolarization in turn activated voltage-gated Ca2+ channels and increased intracellular Ca2+ concentrations in STC-1 cells. 5 In accordance with the observed membrane depolarization and activation of voltage-gated Ca2+ channels, both GABA and muscimol stimulated Ca2+-dependent CCK release. In contrast, bicuculline inhibited the GABA-induced secretion of CCK. 6 Using the reverse transcription-polymerase chain reaction (RT-PCR), mRNA of the GABAA receptor subunits α2, α3, α5, β1, β3 and δ could be detected in STC-1 cells. 7 In summary, we have shown that the CCK-secreting gut NE cell line STC-1 expresses functional GABAA receptors and that GABA stimulates CCK release. Thus, GABA is involved in the fine tuning of CCK secretion from the gut NE cell line STC-1.