title: Pharmacological aspects of anticancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity.
abstract: Cytotoxic drug-induced nausea and vomiting are the side effects most feared by cancer patients. Emesis is an instinctive defense reaction caused by the somatoautonomic nerve reflex, which is integrated in the medulla oblongata. Emesis caused by cytotoxic drugs such as cisplatin is associated with an increase in the concentration of 5-hydroxytryptamine (5-HT) in the intestine and the brainstem. It is proposed that cytotoxic drugs evoke 5-HT release from the enterochromaffin (EC) cells in the intestinal mucosa and that the released 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 seems to mediate the cisplatin-induced emesis sensitive to 5-HT(3) receptor antagonists. The release of 5-HT from the EC cells, however, is regulated by polymodal mechanisms on autoreceptors or heteroreceptors. The precise role of 5-HT on the occurrence of vomiting has not been fully elucidated. The present review aims to describe the role of 5-HT in anticancer drug-induced emesis from the viewpoint of 5-HT release and afferent vagus nerve activity. Various methods for predicting emesis are also evaluated.
authors.affiliation: Department of Pharmacology, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Kanazawa, Japan. minami@hoku-iryo-u.ac.jp
authors.forename: Masaru
authors.initials: M
authors.lastname: Minami
authors.forename: Toru
authors.initials: T
authors.lastname: Endo
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirafuji
authors.forename: Naoya
authors.initials: N
authors.lastname: Hamaue
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Liu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hiroshige
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nemoto
authors.forename: Hideya
authors.initials: H
authors.lastname: Saito
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D004759:Enterochromaffin Cells / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D012701:Serotonin / Q000097:blood / Q000378:metabolism* / Q000652:urine; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*; D014839:Vomiting / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D000970:Antineoplastic Agents; D012701:Serotonin