Extracellular CGMP Reduces the Excitability of Sensory Dorsal Root Ganglion Neurons via an Extracellular Mechanism

Luke A. Grundy; Joel Castro; Andrea Harrington; Stefanie Peters; Robert Feil; Paul Miller; Andre Ghetti; Gerhard Hannig; Caroline Kurtz; Ada Silos-Santiago; Stuart Brierley

doi:10.1016/S0016-5085(17)30847-8

Extracellular CGMP Reduces the Excitability of Sensory Dorsal Root Ganglion Neurons via an Extracellular Mechanism

Luke A. Grundy, Joel Castro, Andrea Harrington, Stefanie Peters, Robert Feil, Paul Miller, Andre Ghetti, Gerhard Hannig, Caroline Kurtz, Ada Silos-Santiago, Stuart Brierley

Research output: Contribution to journal › Meeting Abstract › peer-review

Abstract

Linaclotide, a guanylate cyclase-C (GC-C) agonist, reduces abdominal pain and improves constipation in patients with Irritable Bowel Syndrome with constipation (IBS-C). Cyclic GMP (cGMP) is a second messenger produced in, and released from, intestinal epithelial cells in response to GC-C activation. We have recently shown that both linaclotide and exogenous extracellular cGMP inhibit colonic nociceptor mechanosensitivity with greater efficacy during chronic visceral hypersensitivity (CVH) relative to healthy controls. However, the effects of linaclotide and exogenous cGMP on isolated sensory dorsal root ganglion (DRG) neuron excitability remain to be determined.

Original language	English
Pages (from-to)	S-156
Number of pages	1
Journal	Gastroenterology
Volume	152
Issue number	5, Supplement 1
DOIs	https://doi.org/10.1016/S0016-5085(17)30847-8
Publication status	Published - Apr 2017
Event	Digestive Disease Week (DDW2017) - McCormick Place, Chicago, United States Duration: 6 May 2017 → 9 May 2017

Keywords

Linaclotide
Guanylate cyclase C
sensory dorsal root ganglion
IBS-C
cGMP
DRG
dorsal root ganglion
CVH
Chronic visceral pain

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@article{452d5bd170c14d41b6165e9b366f9025,

title = "Extracellular CGMP Reduces the Excitability of Sensory Dorsal Root Ganglion Neurons via an Extracellular Mechanism",

abstract = "Linaclotide, a guanylate cyclase-C (GC-C) agonist, reduces abdominal pain and improves constipation in patients with Irritable Bowel Syndrome with constipation (IBS-C). Cyclic GMP (cGMP) is a second messenger produced in, and released from, intestinal epithelial cells in response to GC-C activation. We have recently shown that both linaclotide and exogenous extracellular cGMP inhibit colonic nociceptor mechanosensitivity with greater efficacy during chronic visceral hypersensitivity (CVH) relative to healthy controls. However, the effects of linaclotide and exogenous cGMP on isolated sensory dorsal root ganglion (DRG) neuron excitability remain to be determined. ",

keywords = "Linaclotide, Guanylate cyclase C, sensory dorsal root ganglion, IBS-C, cGMP, DRG, dorsal root ganglion, CVH, Chronic visceral pain",

author = "Grundy, {Luke A.} and Joel Castro and Andrea Harrington and Stefanie Peters and Robert Feil and Paul Miller and Andre Ghetti and Gerhard Hannig and Caroline Kurtz and Ada Silos-Santiago and Stuart Brierley",

year = "2017",

month = apr,

doi = "10.1016/S0016-5085(17)30847-8",

language = "English",

volume = "152",

pages = "S--156",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Co.",

number = "5, Supplement 1",

note = "Digestive Disease Week (DDW2017) ; Conference date: 06-05-2017 Through 09-05-2017",

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TY - JOUR

T1 - Extracellular CGMP Reduces the Excitability of Sensory Dorsal Root Ganglion Neurons via an Extracellular Mechanism

AU - Grundy, Luke A.

AU - Castro, Joel

AU - Harrington, Andrea

AU - Peters, Stefanie

AU - Feil, Robert

AU - Miller, Paul

AU - Ghetti, Andre

AU - Hannig, Gerhard

AU - Kurtz, Caroline

AU - Silos-Santiago, Ada

AU - Brierley, Stuart

PY - 2017/4

Y1 - 2017/4

N2 - Linaclotide, a guanylate cyclase-C (GC-C) agonist, reduces abdominal pain and improves constipation in patients with Irritable Bowel Syndrome with constipation (IBS-C). Cyclic GMP (cGMP) is a second messenger produced in, and released from, intestinal epithelial cells in response to GC-C activation. We have recently shown that both linaclotide and exogenous extracellular cGMP inhibit colonic nociceptor mechanosensitivity with greater efficacy during chronic visceral hypersensitivity (CVH) relative to healthy controls. However, the effects of linaclotide and exogenous cGMP on isolated sensory dorsal root ganglion (DRG) neuron excitability remain to be determined.

AB - Linaclotide, a guanylate cyclase-C (GC-C) agonist, reduces abdominal pain and improves constipation in patients with Irritable Bowel Syndrome with constipation (IBS-C). Cyclic GMP (cGMP) is a second messenger produced in, and released from, intestinal epithelial cells in response to GC-C activation. We have recently shown that both linaclotide and exogenous extracellular cGMP inhibit colonic nociceptor mechanosensitivity with greater efficacy during chronic visceral hypersensitivity (CVH) relative to healthy controls. However, the effects of linaclotide and exogenous cGMP on isolated sensory dorsal root ganglion (DRG) neuron excitability remain to be determined.

KW - Linaclotide

KW - Guanylate cyclase C

KW - sensory dorsal root ganglion

KW - IBS-C

KW - cGMP

KW - DRG

KW - dorsal root ganglion

KW - CVH

KW - Chronic visceral pain

U2 - 10.1016/S0016-5085(17)30847-8

DO - 10.1016/S0016-5085(17)30847-8

M3 - Meeting Abstract

VL - 152

SP - S-156

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 5, Supplement 1

T2 - Digestive Disease Week (DDW2017)

Y2 - 6 May 2017 through 9 May 2017

ER -

Extracellular CGMP Reduces the Excitability of Sensory Dorsal Root Ganglion Neurons via an Extracellular Mechanism

Abstract

Keywords

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