Effect of GABA(B) receptor agonist on distension-sensitive pelvic nerve afferent fibers innervating rat colon.
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.
Sengupta
Jyoti N
JN
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. sengupta@mcw.edu
Medda
Bidyut K
BK
Shaker
Reza
R
D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D003106:Colon / Q000294:innervation* / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010388:Pelvis / Q000294:innervation; D010812:Physical Stimulation; D011312:Pressure; D051381:Rats; D020318:Rats, Long-Evans; D018080:Receptors, GABA-B / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000601:surgery
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C107353:CGP 54626; D001418:Baclofen