[Role of serotonin in emesis].
There are now abundant evidence to confirm the role of serotonin (5-HT) and in particular, 5-HT3 receptors in the control of cisplatin-induced emesis. Emesis caused by cisplatin is associated with an increase in the concentration of 5-HT in the intestinal mucosa and in the area postrema. The intestinal mucosa contains enterochromaffin (EC) cells that synthesize and secrete approximately 80% of all 5-HT produced in the body. A selective 5-HT3 agonist, 2-methyl-5-HT, induced a dose-dependent increase in 5-HT level from the ileum. Furthermore, a selective 5-HT4-receptor agonist, 5-methoxytryptamine also induced a concentration-dependent increase of 5-HT level. Both 5-HT3 and 5-HT4 receptors may be involved in intestinal 5-HT release. It is proposed that anticancer drugs cause 5-HT release from the EC cells and that the released 5-HT stimulates the 5-HT3 receptors on the afferent vagal fibers, resulting in their deporalization. Electrical stimulation of the abdominal vagal afferents is capable of inducing emesis, and abdominal vagotomy suppresses cisplatin-induced emesis. These results indicate that the vagus is the major afferent pathway involved in the detection of emetic stimuli.
Minami
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
Endo
T
T
Hirafuji
M
M
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D009325:Nausea / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013373:Substance P / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology; D014839:Vomiting / Q000139:chemically induced* / Q000503:physiopathology
D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D013373:Substance P; D002945:Cisplatin