Evaluation of the anti-emetic potential of anti-migraine drugs to prevent resiniferatoxin-induced emesis in Suncus murinus (house musk shrew)

Cheng, Frankie H.M.; Andrews, Paul; Moreaux, Benoit; Ngan, Man-P.; Rudd, John A.; Sam, Tasia S.W.; Wai, Man-K.; Wan, Christina

doi:10.1016/j.ejphar.2004.12.022

Cited by 9 publications

(10 citation statements)

References 52 publications

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“…The proemetic action of TRPV1 activation appears to reverse quickly to an antiemetic action, given that vomiting caused by stimulation of the medial solitary nucleus in the brainstem, radiation, systemic administration of cisplatin, loperamide or apomorphine or intragastric administration of CuSO 4 is depressed by capsaicin and resiniferatoxin (Andrews & Bhandari, 1993; Shiroshita et al, 1997; Andrews et al, 2000; Rudd & Wai, 2001; Yamakuni et al, 2002). Since the mechanism behind the dual proemetic and antiemetic action of TRPV1 agonists is not understood, the existence of a novel vanilloid receptor has been envisaged (Cheng et al, 2005). Non-pungent agonists at TRPV1 such as arvanil, olvanil, anandamide and N-arachidonoyl-dopamine fail to evoke emesis in the ferret but are able to blunt vomiting evoked by morphine-6-glucuronide, apomorphine, cisplatin and CuSO 4 (Sharkey et al, 2007; Chu et al, 2010).…”

Section: Expression and Functional Implications Of Trp Channels In Thmentioning

confidence: 99%

Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

Holzer

2011

Pharmacology & Therapeutics

222

215

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Approximately 20 of the 30 mammalian transient receptor potential (TRP) channel subunits are expressed by specific neurons and cells within the alimentary canal. They subserve important roles in taste, chemesthesis, mechanosensation, pain and hyperalgesia and contribute to the regulation of gastrointestinal motility, absorptive and secretory processes, blood flow, and mucosal homeostasis. In a cellular perspective, TRP channels operate either as primary detectors of chemical and physical stimuli, as secondary transducers of ionotropic or metabotropic receptors, or as ion transport channels. The polymodal sensory function of TRPA1, TRPM5, TRPM8, TRPP2, TRPV1, TRPV3 and TRPV4 enables the digestive system to survey its physical and chemical environment, which is relevant to all processes of digestion. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 contribute to the absorption of Ca2+ and Mg2+, respectively. TRPM7 participates in intestinal pacemaker activity, and TRPC4 transduces muscarinic acetylcholine receptor activation to smooth muscle contraction. Changes in TRP channel expression or function are associated with a variety of diseases/disorders of the digestive system, notably gastro-esophageal reflux disease, inflammatory bowel disease, pain and hyperalgesia in heartburn, functional dyspepsia and irritable bowel syndrome, cholera, hypomagnesemia with secondary hypocalcemia, infantile hypertrophic pyloric stenosis, esophageal, gastrointestinal and pancreatic cancer, and polycystic liver disease. These implications identify TRP channels as promising drug targets for the management of a number of gastrointestinal pathologies. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential.

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Section: Expression and Functional Implications Of Trp Channels In Thmentioning

confidence: 99%

Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

Holzer

2011

Pharmacology & Therapeutics

222

215

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“…Limited evidence that RTX is acting via TRPV1 to induce emesis derives from the ability of the non-selective TRPV1 channel blocker ruthenium red (0.03–3 μmol/kg, s.c. ) to reduce the emetic response to subcutaneous RTX (100 nmol/kg, s.c. ) in a dose related manner. 70 However, the classical TRPV1 receptor antagonist capsazepine was without effect. 70 Ruthenium red (1 or 10 mg/kg s.c. Thirty min before RTX 100 μg/kg.s.c.)…”

Section: Introductionmentioning

confidence: 99%

“… 70 However, the classical TRPV1 receptor antagonist capsazepine was without effect. 70 Ruthenium red (1 or 10 mg/kg s.c. Thirty min before RTX 100 μg/kg.s.c.) blocked the emetic and genital grooming effects of RTX, but did not block the emetic effect of nicotine showing that ruthenium red does not have any broad spectrum anti-emetic effects itself (Toyoda, Suzuki, Otsuka, Woods, Andrews, Matsuki, 2000, unpublished observations).…”

Section: Introductionmentioning

confidence: 99%

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The involvement of TRPV1 in emesis and anti-emesis

et al. 2015

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Diverse transmitter systems (e.g. acetylcholine, dopamine, endocannabinoids, endorphins, glutamate, histamine, 5-hydroxytryptamine, substance P) have been implicated in the pathways by which nausea and vomiting are induced and are targets for anti-emetic drugs (e.g. 5-hydroxytryptamine3 and tachykinin NK1 antagonists). The involvement of TRPV1 in emesis was discovered in the early 1990s and may have been overlooked previously as TRPV1 pharmacology was studied in rodents (mice, rats) lacking an emetic reflex. Acute subcutaneous administration of resiniferatoxin in the ferret, dog and Suncus murinus revealed that it had “broad–spectrum” anti-emetic effects against stimuli acting via both central (vestibular system, area postrema) and peripheral (abdominal vagal afferents) inputs. One of several hypotheses discussed here is that the anti-emetic effect is due to acute depletion of substance P (or another peptide) at a critical site (e.g. nucleus tractus solitarius) in the central emetic pathway. Studies in Suncus murinus revealed a potential for a long lasting (one month) effect against the chemotherapeutic agent cisplatin. Subsequent studies using telemetry in the conscious ferret compared the anti-emetic, hypothermic and hypertensive effects of resiniferatoxin (pungent) and olvanil (non-pungent) and showed that the anti-emetic effect was present (but reduced) with olvanil which although inducing hypothermia it did not have the marked hypertensive effects of resiniferatoxin. The review concludes by discussing general insights into emetic pathways and their pharmacology revealed by these relatively overlooked studies with TRPV1 activators (pungent an non-pungent; high and low lipophilicity) and antagonists and the potential clinical utility of agents targeted at the TRPV1 system.

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“…Suncus has the ability to vomit in response to mild shaking or ingestion of chemicals (Andrews et al, 1996;Ueno et al, 1987). Since rodents including rats and mice do not show an emetic reflex, suncus has been extensively used to examine the mechanism of emetic responses and to develop antiemetic drugs (Andrews et al, 1996;Cheng et al, 2005;Sam et al, 2003;Uchino et al, 2002;Yamamoto et al, 2009). Hempfling et al reported that the suncus esophagus has morphological features similar to those in rats and mice: intrinsic nitrergic nerves innervate motor endplates on striated muscle cells, which is called 'enteric co-innervation' (Hempfling et al, 2009).…”

Section: Functional Aproachesmentioning

confidence: 99%

Neural Regulatory Mechanisms of Esophageal Motility and Its Implication for GERD

Shiina¹,

Shimizu²

2012

Gastroesophageal Reflux Disease

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On the other hand, since neural regulatory mechanisms of esophageal motiliy, especially roles of the intrinsic nervous system in the striated muscle portion, have remained to be clarified (Clouse & Diamant, 2006; Conklin & Christensen, 1994; Goyal & Chaudhury, 2008), little attention has been paid to the relationship between intrinsic neural regulatory mechanisms for esophageal motility and pathophysiology of GERD. Discussion of this relationship is important and might indicate novel therapeutic targets for GERD. In this chapter, we describe neural regulation of the esophageal motility on the basis of results www.intechopen.com Gastroesophageal Reflux Disease 4 of our studies, and we discuss the relationship between pathogenic mechanisms of GERD and esophageal dysmotility.

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Evaluation of the anti-emetic potential of anti-migraine drugs to prevent resiniferatoxin-induced emesis in Suncus murinus (house musk shrew)

Cited by 9 publications

References 52 publications

Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

The involvement of TRPV1 in emesis and anti-emesis

Neural Regulatory Mechanisms of Esophageal Motility and Its Implication for GERD

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