title: The involvement of TRPV1 in emesis and anti-emesis.
abstract: 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.
authors.affiliation: Brain and Mind Institute; Chinese University of Hong Kong; Shatin; New Territories, Hong Kong SAR; School of Biomedical Sciences; Faculty of Medicine; Chinese University of Hong Kong; Shatin; New Territories, Hong Kong SAR.
authors.forename: John A
authors.initials: JA
authors.lastname: Rudd
authors.affiliation: School of Biomedical Sciences and Pharmacy; University of Newcastle ; Callaghan, NSW, Australia.
authors.forename: Eugene
authors.initials: E
authors.lastname: Nalivaiko
authors.affiliation: Laboratory of Chemical Pharmacology; Graduate School of Pharmaceutical Sciences; The University of Tokyo ; Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Matsuki
authors.affiliation: School of Biomedical Sciences; Faculty of Medicine; Chinese University of Hong Kong ; Shatin; New Territories, Hong Kong SAR.
authors.forename: Christina
authors.initials: C
authors.lastname: Wan
authors.affiliation: Division of Biomedical Sciences; St George's University of London ; London, UK.
authors.forename: Paul Lr
authors.initials: PL
authors.lastname: Andrews
keywords: 12-HPETE, 12-hydroperoxy-eicosatetraenoic acid; 5-HT, 5-hydroxytryptamine; 5-HT3, 5-hdroxytryptamine3; 8-OH-DPAT, (±)-8-Hydroxy-2-dipropylaminotetralin; AM404; AM404, N-arachidonoylaminophenol; AMT, anandamide membrane transporter; AP, area postrema; BBB, blood brain barrier; CB1, cannabinoid1; CGRP, calcitonin gene-related peptide; CINV, chemotherapy-induced nausea and vomiting; CP 99,994; CTA, conditioned taste aversion; CVO's, circumventricular organs; D2, dopamine2; DRG, dorsal root ganglia; FAAH, fatty acid amide hydrolase; H1, histamine1; LTB4, leukotriene B4; NADA, N-arachidonoyl-dopamine; NK1, neurokinin1; POAH, preoptic anterior hypothalamus; RTX; Suncus murinus; TRPV1; TRPV1, transient receptor potential vanilloid receptor1; anti-emetic; capsaicin; ferret; i.v., intravenous; nausea; olvanil; thermoregulation; vanilloid; vomiting