Functional significance of a newly discovered neuropeptide, orphanin FQ, in rat gastrointestinal motility

Yazdani, Ali; Takahashi, Toshio; Bagnol, Didier; Watson, Stanley J.; Owyang, Chung

doi:10.1016/s0016-5085(99)70234-9

Cited by 52 publications

(42 citation statements)

References 25 publications

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“…Circular muscle strips were isolated from the proximal colon. As previously described (25,27), circular muscle strips (10 ϫ 3 mm) obtained from the proximal colon were suspended between two platinum electrodes in a 30-ml organ bath filled with Krebs-Henseleit buffer containing 0.1% BSA. Fig.…”

Section: Methodsmentioning

confidence: 99%

Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats

Tsukamoto

Nakade²,

Mantyh³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Corticotropin releasing factor (CRF) is one of the most important factors in the mechanism of stress-induced stimulation of colonic motility. However, it is controversial whether stress-induced stimulation of colonic motility is mediated via central or peripheral CRF receptors. We investigated the hypothesis that peripherally injected CRF accelerates colonic motility through the central CRF receptor, but not the peripheral CRF receptor. A strain gauge transducer was sutured on the serosal surface of the proximal colon. Colonic motility was monitored before and after the peripheral injection of CRF. An in vitro muscle strip study was also performed to investigate the peripheral effects of CRF. Subcutaneous injection of CRF (30 -100 g/kg) stimulated colonic motility in a dose-dependent manner. The stimulatory effect of peripherally administered CRF on colonic motility was abolished by truncal vagotomy, hexamethonium, atropine, and intracisternal injection of astressin (a CRF receptor antagonist). No responses to CRF (10 Ϫ9 Ϫ10 Ϫ7 M) of the muscle strips of the proximal colon were observed. These results suggest that the stimulatory effect of colonic motility in response to peripheral administration of CRF is mediated by the vagus nerve, nicotinic receptors, muscarinic receptors, and CRF receptors of the brain stem. It is concluded that peripherally administered CRF reaches the area postrema and activates the dorsal nucleus of vagi via central CRF receptors, resulting in stimulation of the vagal efferent and cholinergic transmission of the proximal colon.vagal efferent THERE IS ACCUMULATED EVIDENCE that stress stimulates the release of corticotropin releasing factor (CRF) from the paraventricular nucleus and that released CRF stimulates colonic motor activity. However, it is controversial whether CRF-induced acceleration of colonic motility is mediated via central CRF receptors (4) or peripheral CRF receptors (3). Stress or centrally injected CRF stimulates colonic motor function by cerebral CRF receptors (10,22). The stimulatory effect of centrally administered CRF on colonic transit is abolished by truncal vagotomy (9). Electrophysiological study demonstrated that CRF stimulates the dorsal motor nucleus of the vagus nerve (DMV) in vivo and in vitro (11). Stress-induced stimulation of defecatory response is antagonized by the central administration of a CRF antagonist, but not by the peripheral administration of a CRF antagonist (16). These reports indicated that centrally released CRF induced by stress stimulates vagal efferent, resulting in stimulation of colonic motility and transit.In contrast, others showed that peripherally administered CRF stimulates colonic motility via its own peripheral receptor, and the stimulatory effect of CRF is antagonized by peripheral injection of CRF antagonists (13,14,26). Restraint stress-induced stimulation of fecal pellet output is antagonized by the peripheral administration of a CRF antagonist (26). CRF-producing cells are present in the colonic mucosa (7,19). It is propose...

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Section: Methodsmentioning

confidence: 99%

Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats

Tsukamoto

Nakade²,

Mantyh³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…No other structures apart from neurons appear to be stained. results are often contradictory, depending on the site of administration, dose used and the animal model employed in the study [23,26,35,36] . Our observations in vivo clearly showed a differential, ORL1-dependent action of nociceptin in the mouse ileum and colon, where it accelerates and decreases the intestinal motility, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Using specific antibodies, nociceptin has previously been localized mainly on fibers of myenteric neurons of rat colon and neuronal cell bodies of guinea pig colon [9,36] . Our study extends these observations to mouse colon and for the first time reports that nociceptin appears to be present in vesicles in the cell body of the majority of myenteric neurons, where it double labels with NOS and PGP9.5.…”

Section: Discussionmentioning

confidence: 99%

Nociceptin effect on intestinal motility depends on opioid-receptor like-1 receptors and nitric oxide synthase co-localization

Sibaev

Fichna

Saur

et al. 2015

WJGPT

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Author contributions: Sibaev A, Fichna J, Saur D, Yuece B, Timmermans JP and Storr M contributed to study concept and design; Sibaev A, Fichna J, Saur D and Timmermans JP contributed to acquisition of data; all authors contributed to analysis and interpretation of data; Storr M contributed to drafting of the manuscript; all authors contributed to critical revision of the manuscript for important intellectual content; Sibaev A and Fichna J contributed to statistical analysis; Timmermans JP and Storr M contributed to study supervision. Nociceptin effect on intestinal motility depends on opioidreceptor like-1 receptors and nitric oxide synthase colocalization Basic StudyORIGINAL ARTICLE myenteric neurotransmission and motility. METHODS:Reverse transcriptase -polymerase chain reaction and immunohistochemistry were used to localize nociceptin and ORL1 in mouse tissues. Intracellular electrophysiological recordings of excitatory and inhibitory junction potentials (EJP, IJP) were made in a chambered organ bath. Intestinal motility was measured in vivo . RESULTS:Nociceptin accelerated whole and upper GI transit, but slowed colonic expulsion in vivo in an ORL1-dependent manner, as shown using [Nphe 1 ]NOC and AS ODN pretreatment. ORL1 and nociceptin immunoreactivity were found on enteric neurons. Nociceptin reduced the EJP and the nitric oxide-sensitive slow IJP in an ORL1-dependent manner, whereas the fast IJP was unchanged. Nociceptin further reduced the spatial spreading of the EJP up to 2 cm. CONCLUSION:Compounds acting at ORL1 are good candidates for the future treatment of disorders associated with increased colonic transit, such as diarrhea or diarrhea-predominant irritable bowel syndrome. Core tip: Here we aimed to study the effect of the endogenous opioid-receptor like-1 (ORL1) agonist nociceptin on gastrointestinal (GI) myenteric neurotransmission and motility. We observed that nociceptin reduces excitatory and inhibitory neurotransmission in motorneurons and interneurons and the overall effect on the GI tract may depend on co-localization of ORL1 receptors with nitric oxide synthase. Since ORL1 activation, unlike other opioid receptor-active drugs, is not associated with central side effects, compounds acting at the ORL1 may be good candidates for the future treatment of disorders associated with increased colonic transit, such as diarrhea or diarrhea-predominant irritable bowel syndrome.

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“…Accordingly, the NOP receptor has been identified in the central and peripheral nervous systems and along the entire gastrointestinal tract of the rat (13,14). Nerve fibers immunoreactive to N/OFQ were found in the myenteric plexus and circular muscle layer of the rat colon (7).…”

Section: N Ociceptin/orphanin Fq (N/ofq) Is a Heptade-mentioning

confidence: 99%

“…Since the early studies, it became evident that N/OFQ was involved in modulation of pain, anxiety, feeding, and memory processes (3)(4)(5)(6). Central and peripheral administration of the peptide has also been reported to exert multiple effects in the gastrointestinal tract, affecting gastric and intestinal motility (7)(8)(9) and secretion (10,11).…”

Section: N Ociceptin/orphanin Fq (N/ofq) Is a Heptade-mentioning

confidence: 99%

Peripheral Mechanisms Involved in Gastric Mucosal Protection by Intracerebroventricular and Intraperitoneal Nociceptin in Rats

et al. 2005

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Nociceptin (N/OFQ) exerts multiple effects in the gastrointestinal tract after central or peripheral administration. In the present study, we examined the possible peripheral mechanisms mediating gastric protection by N/OFQ in rats. Gastric mucosal lesions were induced by 50% ethanol (1 ml/rat intragastrically). N/OFQ, administered either intracerebroventricularly (3 g/rat) or ip (10 g/kg), significantly reduced macroscopic and histological damage. capeptide, isolated from brain extract, which shows a structural homology to the opioid peptide dynorphin A and binds to the orphan opioid receptor-like 1 receptor, now termed NOP receptor (1, 2). Since the early studies, it became evident that N/OFQ was involved in modulation of pain, anxiety, feeding, and memory processes (3-6). Central and peripheral administration of the peptide has also been reported to exert multiple effects in the gastrointestinal tract, affecting gastric and intestinal motility (7-9) and secretion (10, 11).We have recently shown that N/OFQ protects against gastric mucosal damage induced by intragastric (ig) ethanol exposure in the rat and that its effect that is reversed by the selective antagonist UFP-101, suggesting the peptide exerts gastric protection through the NOP receptor (12). The evidence that N/OFQ protects the gastric mucosa after both central and peripheral administration suggests that the peptide interacts with distinct central and peripheral pathways. Accordingly, the NOP receptor has been identified in the central and peripheral nervous systems and along the entire gastrointestinal tract of the rat (13,14). Nerve fibers immunoreactive to N/OFQ were found in the myenteric plexus and circular muscle layer of the rat colon (7).Resistance of the gastric mucosa against damage by endogenous and exogenous aggressors is ensured by a complex system of mediators. A crucial role has been attributed to the neuropeptide calcitonin gene-related peptide (CGRP), released by capsaicin-sensitive extrinsic nerve fibers and to nitric oxide (NO), synthesized by the neuronal and endothelial enzymes. The sensory neuropeptide and NO appear to act in concert in the modulation of mucosal integrity (15,16). There is also evidence for an interaction between autonomic nervous system and peripheral CGRP/NO pathways (17). Indeed, neuropeptides like TRH, peptide YY (PYY), and adrenomedullin, acting at the central level, reduce gastric lesions caused by ethanol in rats through vagal cholinergic pathways associated with peripheral release of CGRP and activation of .The present study was aimed to further characterize the protective activity of N/OFQ, injected centrally or peripherally, against ethanol damage in rats, by evaluating the possible peripheral neural mechanisms mediating the effect of the peptide. In particular, we have examined the role of NO and of afferent nerve fibers as well as of parasympathetic and sympathetic systems. Materials and Methods AnimalsMale Wistar rats, weighing 180 -200 g (Harlan, S. Pietro al Natisone, Italy) were individually hou...

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Functional significance of a newly discovered neuropeptide, orphanin FQ, in rat gastrointestinal motility

Cited by 52 publications

References 25 publications

Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats

Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats

Nociceptin effect on intestinal motility depends on opioid-receptor like-1 receptors and nitric oxide synthase co-localization

Peripheral Mechanisms Involved in Gastric Mucosal Protection by Intracerebroventricular and Intraperitoneal Nociceptin in Rats

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