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 innervations of the gut, where GABA stimulates motor neurons, and non-neural cells 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 chloride channel constructed from different subunit families (alpha, beta, gamma, delta, epsilon). In rat these exist as subtypes, alpha1-6, beta1-3, gamma1-3 and delta, defining the clinically relevant pharmacological features of GABA(A) receptors. However, the identity, distribution, and abundance of enteric GABA(A) receptor subunits are unknown. To identify and map the regional expression of GABA(A) receptor subunit messenger RNAs in the enteric nervous system, we assayed enteric RNA from the ileum of Sprague-Dawley rats by reverse transcription-polymerase chain reaction for alpha1-6, beta 1-3, gamma1-3, and delta subunit messenger RNAs. Subunit messenger RNA localization, was probed by in situ hybridization. Reverse transcription-polymerase chain reaction analysis of RNA from myenteric and submucosal nerve layers revealed the expression alpha1, alpha3, beta2, beta3, gamma1 and gamma3 subunit messenger RNAs. Little alpha4 and alpha6 and no alpha2, beta1, gamma2 or delta subunit messenger RNA were detected. In situ hybridization revealed that transcripts for alpha1, alpha3, alpha5 and beta2 subunits occur in both myenteric and submucous ganglia. However, beta3 messenger RNA was found only in myenteric plexus. The gamma1 subunit messenger RNA was also restricted to the cells in the myenteric plexus while gamma3 was found in cells of both nerve layers. In this study of the subunit messenger RNA expression profile of GABA(A) receptors within the enteric nerve layers we show an abundant, diverse and widespread distribution that is unique in comparison to the CNS. The distinctive and heterogeneous distribution of enteric GABA(A) subunits may be important in the integration of neural control of gut function.
Poulter
M O
MO
Laboratory of Molecular Neuropharmacology, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Singhal
R
R
Brown
L A
LA
Krantis
A
A
D000818:Animals; D018118:Chloride Channels / Q000502:physiology; D017615:Enteric Nervous System / Q000166:cytology / Q000378:metabolism*; D005725:Ganglia, Autonomic / Q000166:cytology / Q000378:metabolism; D007082:Ileum / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000145:classification / Q000235:genetics* / Q000502:physiology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000145:classification / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018118:Chloride Channels; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011963:Receptors, GABA-A