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

J Pharmacol Sci. 2004 Apr;94(4):368-75. doi: 10.1254/jphs.94.368.

Abstract

Characterization of the gamma-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Baclofen / pharmacology
  • Benzoates / pharmacology
  • Dimerization
  • Dogs
  • Female
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • Gastrointestinal Motility / drug effects*
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Male
  • Microdialysis*
  • Muscimol / pharmacology
  • Organophosphorus Compounds / pharmacology
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, GABA-B / analysis
  • Receptors, GABA-B / genetics
  • Receptors, GABA-B / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Benzoates
  • CGP 62349
  • GABA Agonists
  • GABA Antagonists
  • Organophosphorus Compounds
  • RNA, Messenger
  • Receptors, GABA-B
  • Muscimol
  • Baclofen
  • Acetylcholine