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Updated: Sep 16, 2026
Gastrointestinal Motility Monitor (GIMM)
Published on: December 2, 2010
Orphanin FQ causes contractions via inhibiting purinergic pathway in the rat colon
T Takahashi1, D Bagnol, D Schneider
1Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Background & Aims:
We have previously shown that orphanin FQ (OFQ) preferentially stimulates muscle contraction in the rat colon. However, the mechanism of action of OFQ remains unclear.
Methods:
We studied the effects of OFQ on muscle contractions and inhibitory junction potentials (IJPs) in rat colon. The site of action of OFQ was also investigated by in situ hybridization of OFQ receptors.
Results:
OFQ (10(-10) to 10(-6) mol/L) caused circular muscle contractions that were blocked by tetrodotoxin (10(-7) mol/L), suggesting the contractions were nerve mediated. Suramin (a nonselective P(2)-purinoceptor antagonist; 10(-4) mol/L) and reactive blue 2 (a P(2Y)-purinoceptor antagonist; 3 x 10(-5) mol/L), but not pyridoxalphosphate-6-azophenyl-2',4' disulfonic acid (PPADS; a P(2X)-purinoceptor antagonist; 3 x 10(-5) mol/L), abolished OFQ-induced colonic contractions. Focal stimulation of interganglionic fiber tracts evoked biphasic IJPs in colonic circular muscle cells. Suramin and reactive blue 2 inhibited the peak amplitude of the IJP, whereas PPADS had no effect. Cumulative addition of OFQ (10(-10) to 10(-6 )mol/L) significantly inhibited the IJPs. In situ hybridization revealed that OFQ receptor messenger RNA was expressed in the colonic myenteric plexus but not in the smooth muscle cells, suggesting that the site of action of OFQ is neuronal.
Conclusions:
These results suggest that OFQ causes muscle contractions by inhibiting purinergic inhibitory motorneurons in the rat colon.
Insights
Orphanin FQ (OFQ) stimulates rat colon muscle contractions by inhibiting nerve-mediated inhibitory potentials. This action involves blocking P2Y-purinoceptors on neurons, not muscle cells, revealing OFQ
Area of Science:
- Gastroenterology
- Neuropharmacology
- Smooth Muscle Physiology
Background:
- Orphanin FQ (OFQ) is known to stimulate muscle contraction in the rat colon.
- The precise mechanism underlying OFQ's action in the colon remains to be elucidated.
Purpose of the Study:
- To investigate the mechanism of action of orphanin FQ (OFQ) on colonic muscle contractions.
- To determine the site of action of OFQ in the rat colon.
Main Methods:
- Studied the effects of OFQ on colonic muscle contractions and inhibitory junction potentials (IJPs).
- Investigated the site of action using in situ hybridization for OFQ receptors.
- Utilized purinoceptor antagonists (Suramin, Reactive Blue 2, PPADS) and tetrodotoxin.
Main Results:
- OFQ induced nerve-mediated circular muscle contractions.
- OFQ-induced contractions and IJPs were inhibited by P2Y-purinoceptor antagonists Suramin and Reactive Blue 2.
- OFQ receptor mRNA was localized to the myenteric plexus neurons, not smooth muscle cells.
Conclusions:
- OFQ stimulates colonic muscle contractions by inhibiting purinergic inhibitory motor neurons.
- The action of OFQ is neuronal, mediated via P2Y-purinoceptors on these inhibitory motor neurons.
