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Effect of GABA(B) receptor agonist on distension-sensitive pelvic nerve afferent fibers innervating rat colon. Am J Physiol Gastrointest Liver Physiol 2002 Dec;283(6):G1343-51

Date

10/22/2002

Pubmed ID

12388205

DOI

10.1152/ajpgi.00124.2002

Scopus ID

2-s2.0-0036890502 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

Spinal afferents innervating the gastrointestinal tract are the major pathways for visceral nociception. Many centrally acting analgesic drugs attenuate responses of visceral primary afferent fibers by acting at the peripheral site. Gamma-amino butyric acid (GABA), a major inhibitory neurotransmitter, acts via metobotropic GABA(B) and ionotropic GABA(A)/GABA(C) receptors. The aim of this study was to test the peripheral effect of selective GABA(B) receptor agonist baclofen on responses of the pelvic nerve afferent fibers innervating the colon of the rat. Distension-sensitive pelvic nerve afferent fibers were recorded from the S(1) sacral dorsal root in anesthetized rats. The effect of baclofen (1-300 micromol/kg) was tested on responses of these fibers to colorectal distension (CRD; 60 mmHg, 30 s). A total of 21 pelvic nerve afferent fibers was recorded. Mechanosensitive properties of four fibers were also recorded before and after bilateral transections of T(12)-S(3) ventral roots (VR). Effect of baclofen was tested on 15 fibers (7 in intact rats, 4 in rats with transected VR, and 4 in rats pretreated with CGP 54626). In nine fibers (5/7 in intact and 4/4 in VR transected rats), baclofen produced dose-dependent inhibition of response to CRD. Pretreatment with selective GABA(B) receptor antagonist CGP 54626 (1 micromol/kg) reversed the inhibitory effect of baclofen. Results suggest a peripheral role of GABA(B) receptors in the inhibition of mechanotransduction property of distension-sensitive pelvic nerve afferent fibers.

Author List

Sengupta JN, Medda BK, Shaker R

Authors

Bidyut K. Medda PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin
Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Afferent Pathways
Animals
Baclofen
Biomechanical Phenomena
Colon
GABA Agonists
GABA Antagonists
GABA-B Receptor Agonists
Male
Nerve Fibers
Organophosphorus Compounds
Pelvis
Physical Stimulation
Pressure
Rats
Rats, Long-Evans
Receptors, GABA-B
Spinal Nerve Roots