The emetic and anti-emetic effects of the capsaicin analogue resiniferatoxin in Suncus murinus, the house musk shrew.
1. In SUNCUS: murinus the ultrapotent capsaicin analogue resiniferatoxin (RTX) induced an emetic response in the dose range 1 - 1000 microg kg(-1), s.c. The latency was inversely related to dose and ranged from 41.2+/-4.4 min. (1 microg kg(-1), s.c.) to 2.7+/-0.6 min. (1000 microg kg(-1), s.c.). 2. The emetic response to RTX (10 or 100 microg kg(-1), s.c.) was blocked or markedly reduced by pre-treatment with RTX (100 microg kg(-1), s.c.), 8-OH-DPAT (100 microg kg(-1), s.c.), morphine (2 mg kg(-1), s.c.), neonatal capsaicin (100 mg kg(-1), s.c.) and the NK(1) receptor antagonist CP-99,994 (10 - 20 mg kg(-1), s.c.) but not by the 5-HT(3) receptor antagonist tropisetron (200 microg kg(-1), s.c.). 3. RTX (100 microg kg(-1), s.c.) induced c-fos-like immunoreactivity in the area postrema and parts of the nucleus tractus solitarius. This pattern is consistent with the proposal that the emetic effect is mediated via one or both of these structures and an involvement of substance P is discussed. 4. RTX (10 and 100 microg kg(-1), s.c.) had broad-spectrum antiemetic effects in Suncus as indicated by its ability to block or markedly reduce the emetic response to motion (1 Hz, 4 cm lateral, 10 min.), cisplatin (20 mg kg(-1), i.p.), intragastric copper sulphate (40 mg kg(-1), p.o.), nicotine (10 mg kg(-1), s.c.) and RTX (100 microg kg(-1), s.c.) itself. 5. It is proposed that the site of the anti-emetic effect is in the nucleus tractus solitarius and mechanisms involving the modulation of substance P release are discussed. 6. The general utility of SUNCUS: for investigations of vanilloid receptors is reviewed in the light of the exquisite sensitivity of the emetic reflex in this species to resiniferatoxin.
Andrews
P L
PL
Department of Physiology, St. George's Hospital Medical School, Cranmer Terrace, London. physical@sghms.ac.uk
Okada
F
F
Woods
A J
AJ
Hagiwara
H
H
Kakaimoto
S
S
Toyoda
M
M
Matsuki
N
N
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000005:Abdomen; D000818:Animals; D000831:Animals, Newborn; D000932:Antiemetics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives; D002945:Cisplatin / Q000009:adverse effects; D019327:Copper Sulfate / Q000009:adverse effects; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000737:chemistry / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology; D009041:Motion Sickness / Q000209:etiology / Q000517:prevention & control; D009538:Nicotine / Q000009:adverse effects; D010880:Piperidines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012788:Shrews; D000077526:Tropisetron; D014628:Vagotomy; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D004224:Diterpenes; D007211:Indoles; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D017366:Serotonin Receptor Agonists; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D000077526:Tropisetron; D009538:Nicotine; D009020:Morphine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C024353:resiniferatoxin; D019327:Copper Sulfate; D002945:Cisplatin; D002211:Capsaicin