GABA(A) receptor subunit messenger RNA expression in the enteric nervous system of the rat: Implications for functional diversity of enteric GABA(A) receptors

GABAergic neurons occur in the myenteric plexus and submucosa and their inn ervations of the gut, where GABA stimulates motor neurons, and non-neural c ells via "central type" GABA(A) receptors. These receptors occur on half of the neurons in the rat intestine. The GABA(A) receptor is a ligand-gated c hloride channel constructed from different subunit families (alpha, beta, g amma, delta, epsilon). In rat these exist as subtypes, (alpha(1-6), beta(1- 3), gamma(1-3) and delta, defining the clinically relevant pharmacological features of GABA(A) receptors. However, the identity, distribution, and abu ndance of enteric GABA(A) receptor subunits are unknown. To identify and ma p the regional expression of GABA(A) receptor subunit messenger RNAs in the enteric nervous system, we assayed enteric RNA from the ileum of Sprague-D awley rats by reverse transcription-polymerase chain reaction for (alpha(1- 6), beta(1-3), gamma(1-3), and delta subunit messenger RNAs. Subunit messen ger RNA localization, was probed by in situ hybridization. Reverse transcri ption-polymerase chain reaction analysis of RNA from myenteric and submucos al nerve layers revealed the expression alpha(1), alpha(3), alpha(5), beta( 2), beta(3), gamma(1) and gamma(3) subunit messenger RNAs. Little alpha(4) and alpha(6) and no alpha(2), beta(1), gamma(2) or delta subunit messenger RNA were detected. In situ hybridization revealed that transcripts for alph a(1), alpha(3), alpha(5) and beta(2) subunits occur in both myenteric and s ubmucous ganglia. However, beta(3) messenger RNA was found only in myenteri c plexus. The gamma(1) subunit messenger RNA was also restricted to the cel ls in the myenteric plexus while gamma(3) was found in cells of both nerve layers. In this study of the subunit messenger RNA expression profile of GABA(A) re ceptors within the enteric nerve layers we show an abundant, diverse and wi despread distribution that is unique in comparison to the CNS. The distinct ive and heterogeneous distribution of enteric GABA(A) subunits may be impor tant in the integration of neural control of gut function. Crown copyright (C) 1999. Published by Elsevier Science Ltd.