The locations of serotonin-3 (5-HT3) receptors involved in initiating
vomiting (
emesis) were assessed by cutting visceral afferents or lesioning the area postrema. The
5-HT3 receptor agonists
phenylbiguanide (PBG) and
2-methyl-5-HT were shown to induce
vomiting and related
prodromal signs (e.g., licking, swallowing) in nonoperated cats. Two-methyl-5-HT, but not PBG, also usually produced defecation and sometimes urination. Most studies were conducted using PBG, which induced
vomiting in 40/49 (82%) cats at doses of 8.0 mg/kg i.p. or less (thresholds ranged from 2-8 mg/kg, median 5 mg/kg). Latencies to the first episode ranged from 4 to 21 min (median 7.5 min). PBG-induced
vomiting was blocked by the
5-HT3 receptor antagonist
MDL 72222. Lesions of the area postrema had no apparent effect on
vomiting induced by PBG or by electrical stimulation of abdominal vagal afferents. In contrast, the threshold of PBG-induced
vomiting was increased by supradiaphragmatic
vagotomy and greatly increased by splanchnic nerve section. Thus, abdominal visceral afferents, but not the area postrema, play an important role in mediating
vomiting induced by i.p. injection of the
5-HT3 receptor agonist PBG. The mechanisms by which
vomiting is induced by PBG as compared to the
cancer chemotherapeutic
drug cisplatin are discussed.