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.
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.
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.
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.
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.
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.
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.