[Serotonin and anticancer drug-induced emesis].
Cytotoxic drug-induced nausea and vomiting are the side effects most feared by cancer patients. Emesis is an instinctive defense reaction caused by the somato-autonomic nerve reflex, which is integrated in the medulla oblongata. Emesis caused by anticancer drugs is associated with an increase in the concentration of serotonin (5-HT) (5-HT) in the intestinal mucosa and brainstem. 5-HT released from the enterochromaffin (EC) cells, which synthesize and secrete 5-HT, stimulates the 5-HT receptors on the adjacent vagal afferent nerves. The depolarization of the vagal afferent nerves stimulates the vomiting center in the brainstem and eventually induces a vomiting reflex. 5-HT released from EC cells appears to mediate the cisplatin-induced emesis sensitive to 5-HT(3) receptor antagonists. The precise role of 5-HT in the occurrence of vomiting has not been fully elucidated. The present review describes the role of 5-HT in anticancer drug-induced emesis from the viewpoint of 5-HT release and afferent vagal nerve activity. Various models and methods for predicting emesis are also evaluated.
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan. minami-m@touei.or.jp
Masaru
M
Minami
Toru
T
Endo
Naoya
N
Hamaue
Masahiko
M
Hirafuji
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects; D004759:Enterochromaffin Cells / Q000378:metabolism; D017829:Granisetron / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D017294:Ondansetron / Q000494:pharmacology / Q000627:therapeutic use; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D058831:Serotonin 5-HT3 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000077526:Tropisetron; D014630:Vagus Nerve / Q000502:physiology; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control
D000932:Antiemetics; D000970:Antineoplastic Agents; D002945:Cisplatin; D017829:Granisetron; D007211:Indoles; D017294:Ondansetron; D044406:Receptors, Serotonin, 5-HT3; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D058831:Serotonin 5-HT3 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D012702:Serotonin Antagonists; D000077526:Tropisetron