- Title
- The involvement of TRPV1 in emesis and anti-emesis
- Creator
- Rudd, John A.; Nalivaiko, Eugene; Matsuki, Norio; Wan, Christina; Andrews, Paul L. R.
- Relation
- Temperature Vol. 2, Issue 2, p. 258-276
- Publisher Link
- http://dx.doi.org/10.1080/23328940.2015.1043042
- Publisher
- Taylor & Francis
- Resource Type
- journal article
- Date
- 2015
- Description
- 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.
- Subject
- AM404; anti-emetic; vomiting; vanilloid; capsaicin; ferret; naudea; olvanil; RTX; <i>Suncus murinus</i>; thermoregulation; TRPV1
- Identifier
- http://hdl.handle.net/1959.13/1315191
- Identifier
- uon:22910
- Identifier
- ISSN:2332-8940
- Language
- eng
- Full Text
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