Cisplatin acutely reduces 5-hydroxytryptamine-induced vagal depolarization in the rat: protective action of dexamethasone.
The effect of the anti-cancer cytotoxic drug cisplatin on KCl and 5-hydroxytryptamine (5-HT)-induced depolarization in the rat isolated cervical vagus nerve was investigated using the 'grease gap' extracellular recording technique. KCl (10 mM) perfused onto the isolated nerve previously incubated for 2 h in 10 microM cisplatin initiated a d.c. potential of 1.06 +/- 0.09 mV compared to a potential of 1.29 +/- 0.13 mV in control nerves. Perfusion with 5 microM 5-HT produced a markedly reduced depolarization (0.23 +/- 0.02 mV) in cisplatin-treated nerves compared with control nerves (0.42 +/- 0.04 mV, P = 0.005). This effect was enhanced when 5-HT was reapplied 30 min later (0.19 +/- 0.02 mV in cisplatin-treated compared with 0.42 +/- 0.03 mV in controls, P < 0.0001). The inhibitory effect of cisplatin on 5-HT-induced depolarization was found to be significantly (P = 0.004) reduced by the addition of dexamethasone (10 microM) to the incubation buffer (0.34 +/- 0.04 mV). These results are discussed in the light of the emetic and neurotoxic effects of cisplatin and the protective effects of dexamethasone.
Woods
A J
AJ
Department of Physiology, St. George's Hospital Medical School, London, UK.
Andrews
P L
PL
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009325:Nausea / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D013237:Stereoisomerism; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D014839:Vomiting / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control
C034697:transplatin; D012701:Serotonin; D003907:Dexamethasone; D002945:Cisplatin