Characterization of GABA_B Receptors Involved in Inhibition of Motility Associated With Acetylcholine Release in the Dog Small Intestine: Possible Existence of a Heterodimer of GABA_B1 and GABA_B2 Subunits

Abstract

Characterization of the γ-aminobutyric acid (GABA)_B receptor involved in the motility of dog small intestine was analyzed by application of the microdialysis method to the small intestine of the whole body of the dog. The reverse transcription-polymerase chain reaction (RT-PCR) was used. Intraarterial administration of muscimol induced acceleration of motility associated with acetylcholine (ACh) release, these responses being antagonized by bicuculline. Intraarterial administration of baclofen induced inhibition of motility associated with ACh release, these responses being antagonized by CGP62349. GABA induced inhibition of motility associated with decrease in ACh release. CGP62349 alone induced acceleration of motility associated with increase in ACh release. RT-PCR revealed the presence of mRNAs for both subunits of GABA_B receptor, GABA_B1 and GABA_B2, in the dog small intestine, although GABA_B1 subunits were 6 isoforms of GABA_B1 (GABA_B1(a) – GABA_B1(g)), except GABA_B1(d). Thus, the GABA_B receptor located at cholinergic neurons as a heterodimer with subunits of GABA_B1 and GABA_B2 in the dog small intestine operates predominantly relative to the GABA_A receptor in physiological motility.