Galanin receptors in the rat gastrointestinal tract

Galanin functions are mediated by three distinct G-protein-coupled receptors, galanin receptor 1 (GaIR1), GaIR2 and GaIR3, which activate different intracellular signaling pathways. Here, we quantified mRNA levels of GaIR 1, GaIR2 and GaIR3 in the gastrointestinal tract using real time RT-PCR. GaIR1 and GaIR2 mRNAs were detected in all segments with the highest levels in the large intestine and stomach, respectively. GaIR3 mRNA levels were quite low and mostly confined to the colon. We also investigated the effect of galanin 1-16, which has high affinity for GaIR1 and GaIR2 and low affinity for GaIR3 on depolarization-evoked Ca2+ increases in rat cultured myenteric neurons using Ca2+-imaging. Intracellular Ca2+ changes in myenteric neurons were monitored using the Ca2+ sensitive dye, fluo-4, and confocal microscopy. Galanin 1-16 (1 mu M) markedly inhibited the K+-evoked Ca2+ increases in myenteric neurons. In summary, the differential distribution of GalRs supports the hypothesis that the complex effects of galanin in the gastrointestinal tract result from the activation of multiple receptor subtypes. Furthermore, this study confirms the presence of functional GalRs and suggests that galanin modulates transmitter release from myenteric neurons through inhibition of voltage-dependent calcium channels involving a G(i/o)-coupled GaIR. (c) 2005 Elsevier Ltd. All rights reserved.