GABA(B) receptors inhibit mechanosensitivity of primary afferent endings

Amanda J. Page, L. Ashley Blackshaw

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

The modulatory effects of baclofen on the sensitivity of peripheral afferent endings to mechanical stimulation were investigated using an in vitro ferret gastroesophageal vagal afferent preparation. Changes in sensitivity of three types of gastroesophageal vagal afferent endings previously categorized as mucosal, tension, and tension-mucosal (TM) receptors according to their mechanoreceptive field characteristics were investigated. Baclofen (30-200 μM) dose dependently reduced responses of mucosal afferents to mucosal stroking with calibrated von Frey hairs (10-1000 mg). This was reversed by the GABA(B) receptor antagonist SCH50911 (1 μM). TM afferent responses to mucosal stroking (10-1000 mg) were unaffected by baclofen (30-200 μM). However, baclofen (30-200 μM) significantly inhibited the response of 11 of 18 TM afferents to circumferential tension. This was reversed by SCH50911 (1 μM). Baclofen (100 and 200 μM) significantly inhibited the response of all tension receptor afferents to circumferential tension in the lower range (1-3 gm) but not in the higher range (4-7 gm). This inhibition was reversed by SCH50911 (1 μM; n = 3). This study provides the first direct evidence for the inhibitory modulation of peripheral mechanosensory endings by the G-protein-coupled GABA(B) receptor. Inhibition was dose-dependent, pharmacologically reversible, and selective to certain aspects of mechanosensitivity. These findings have important relevance to strategies for selective reduction of sensory input to the CNS at a peripheral site.

LanguageEnglish
Pages8597-8602
Number of pages6
JournalJournal of Neuroscience
Volume19
Issue number19
Publication statusPublished - 1 Oct 1999
Externally publishedYes

Keywords

  • Esophagus
  • Ferret
  • GABA(B) receptors
  • Mechanoreceptors
  • Vagal afferents
  • Visceral afferents

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Page, Amanda J. ; Blackshaw, L. Ashley. / GABA(B) receptors inhibit mechanosensitivity of primary afferent endings. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 19. pp. 8597-8602.
@article{592d08dc33974fc2ba4fa250e778db06,
title = "GABA(B) receptors inhibit mechanosensitivity of primary afferent endings",
abstract = "The modulatory effects of baclofen on the sensitivity of peripheral afferent endings to mechanical stimulation were investigated using an in vitro ferret gastroesophageal vagal afferent preparation. Changes in sensitivity of three types of gastroesophageal vagal afferent endings previously categorized as mucosal, tension, and tension-mucosal (TM) receptors according to their mechanoreceptive field characteristics were investigated. Baclofen (30-200 μM) dose dependently reduced responses of mucosal afferents to mucosal stroking with calibrated von Frey hairs (10-1000 mg). This was reversed by the GABA(B) receptor antagonist SCH50911 (1 μM). TM afferent responses to mucosal stroking (10-1000 mg) were unaffected by baclofen (30-200 μM). However, baclofen (30-200 μM) significantly inhibited the response of 11 of 18 TM afferents to circumferential tension. This was reversed by SCH50911 (1 μM). Baclofen (100 and 200 μM) significantly inhibited the response of all tension receptor afferents to circumferential tension in the lower range (1-3 gm) but not in the higher range (4-7 gm). This inhibition was reversed by SCH50911 (1 μM; n = 3). This study provides the first direct evidence for the inhibitory modulation of peripheral mechanosensory endings by the G-protein-coupled GABA(B) receptor. Inhibition was dose-dependent, pharmacologically reversible, and selective to certain aspects of mechanosensitivity. These findings have important relevance to strategies for selective reduction of sensory input to the CNS at a peripheral site.",
keywords = "Esophagus, Ferret, GABA(B) receptors, Mechanoreceptors, Vagal afferents, Visceral afferents",
author = "Page, {Amanda J.} and Blackshaw, {L. Ashley}",
year = "1999",
month = "10",
day = "1",
language = "English",
volume = "19",
pages = "8597--8602",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "19",

}

Page, AJ & Blackshaw, LA 1999, 'GABA(B) receptors inhibit mechanosensitivity of primary afferent endings', Journal of Neuroscience, vol. 19, no. 19, pp. 8597-8602.

GABA(B) receptors inhibit mechanosensitivity of primary afferent endings. / Page, Amanda J.; Blackshaw, L. Ashley.

In: Journal of Neuroscience, Vol. 19, No. 19, 01.10.1999, p. 8597-8602.

Research output: Contribution to journalArticle

TY - JOUR

T1 - GABA(B) receptors inhibit mechanosensitivity of primary afferent endings

AU - Page, Amanda J.

AU - Blackshaw, L. Ashley

PY - 1999/10/1

Y1 - 1999/10/1

N2 - The modulatory effects of baclofen on the sensitivity of peripheral afferent endings to mechanical stimulation were investigated using an in vitro ferret gastroesophageal vagal afferent preparation. Changes in sensitivity of three types of gastroesophageal vagal afferent endings previously categorized as mucosal, tension, and tension-mucosal (TM) receptors according to their mechanoreceptive field characteristics were investigated. Baclofen (30-200 μM) dose dependently reduced responses of mucosal afferents to mucosal stroking with calibrated von Frey hairs (10-1000 mg). This was reversed by the GABA(B) receptor antagonist SCH50911 (1 μM). TM afferent responses to mucosal stroking (10-1000 mg) were unaffected by baclofen (30-200 μM). However, baclofen (30-200 μM) significantly inhibited the response of 11 of 18 TM afferents to circumferential tension. This was reversed by SCH50911 (1 μM). Baclofen (100 and 200 μM) significantly inhibited the response of all tension receptor afferents to circumferential tension in the lower range (1-3 gm) but not in the higher range (4-7 gm). This inhibition was reversed by SCH50911 (1 μM; n = 3). This study provides the first direct evidence for the inhibitory modulation of peripheral mechanosensory endings by the G-protein-coupled GABA(B) receptor. Inhibition was dose-dependent, pharmacologically reversible, and selective to certain aspects of mechanosensitivity. These findings have important relevance to strategies for selective reduction of sensory input to the CNS at a peripheral site.

AB - The modulatory effects of baclofen on the sensitivity of peripheral afferent endings to mechanical stimulation were investigated using an in vitro ferret gastroesophageal vagal afferent preparation. Changes in sensitivity of three types of gastroesophageal vagal afferent endings previously categorized as mucosal, tension, and tension-mucosal (TM) receptors according to their mechanoreceptive field characteristics were investigated. Baclofen (30-200 μM) dose dependently reduced responses of mucosal afferents to mucosal stroking with calibrated von Frey hairs (10-1000 mg). This was reversed by the GABA(B) receptor antagonist SCH50911 (1 μM). TM afferent responses to mucosal stroking (10-1000 mg) were unaffected by baclofen (30-200 μM). However, baclofen (30-200 μM) significantly inhibited the response of 11 of 18 TM afferents to circumferential tension. This was reversed by SCH50911 (1 μM). Baclofen (100 and 200 μM) significantly inhibited the response of all tension receptor afferents to circumferential tension in the lower range (1-3 gm) but not in the higher range (4-7 gm). This inhibition was reversed by SCH50911 (1 μM; n = 3). This study provides the first direct evidence for the inhibitory modulation of peripheral mechanosensory endings by the G-protein-coupled GABA(B) receptor. Inhibition was dose-dependent, pharmacologically reversible, and selective to certain aspects of mechanosensitivity. These findings have important relevance to strategies for selective reduction of sensory input to the CNS at a peripheral site.

KW - Esophagus

KW - Ferret

KW - GABA(B) receptors

KW - Mechanoreceptors

KW - Vagal afferents

KW - Visceral afferents

UR - http://www.scopus.com/inward/record.url?scp=0033215989&partnerID=8YFLogxK

M3 - Article

VL - 19

SP - 8597

EP - 8602

JO - Journal of Neuroscience

T2 - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 19

ER -