Possible involvement of peripheral 5-HT4 receptors in copper sulfate-induced vomiting in dogs.
The involvement of visceral afferent fibers and 5-HT3 or 5-HT4 receptors in the vomiting induced by oral administration of copper sulfate was investigated in beagle dogs. Vomiting induced by copper sulfate (100 mg/kg) was inhibited markedly by bilateral abdominal vagotomy and bilateral greater splanchnic nerve section. The vomiting induced by copper sulfate was inhibited by blocking 5-HT4 receptors with high doses (1 and 3 mg/kg, i.v.) of ICS 205-930. On the other hand, blocking 5-HT3 receptors with MDL 72222 (0.5 and 5 mg/kg, i.v.) or low doses (0.01 mg/kg i.v.) of ICS 205-930 had no apparent effect on the vomiting induced by copper sulfate. Oral administration of a 5-HT4 receptor agonist, 5-methoxytryptamine (5-MT), caused vomiting at a dose of 100 mg/kg, and the vomiting was inhibited markedly by abdominal visceral nerve section or a high dose (1 mg/kg, i.v.), but not a low dose (0.01 mg/kg, i.v.), of ICS 205-930. Intravenous administration of 5-MT (10 mg/kg) failed to induce vomiting. These results suggest that the abdominal visceral afferent fibers and possibly peripheral 5-HT4 receptors play an important role in the vomiting induced by oral administration of copper sulfate in dogs.
Fukui
H
H
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Yamamoto
M
M
Sasaki
S
S
Sato
S
S
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D003300:Copper / Q000008:administration & dosage / Q000633:toxicity*; D019327:Copper Sulfate; D004285:Dogs; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013153:Splanchnic Nerves / Q000187:drug effects / Q000502:physiology; D014326:Tropanes / Q000494:pharmacology; D000077526:Tropisetron; D014628:Vagotomy; D014781:Viscera / Q000294:innervation; D014839:Vomiting / Q000139:chemically induced*
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D008735:5-Methoxytryptamine; D000077526:Tropisetron; D003300:Copper; D019327:Copper Sulfate; C042253:bemesetron