Substance P and serotonin act synergistically to activate a cation permeability in a neuronal cell line

5‐HT3 receptor antagonism by anpirtoline, a mixed 5‐HT1 receptor agonist/5‐HT3 receptor antagonist

“…Anpirtoline significantly (at least P < 0.05, compared to the respective controls) decreased the number of vomits both in the first 4 h (in the dose-range of 2-10 mg) and in the whole 24 h period (at the doses of 5 and 10mg) after infusion of cisplatin. (Schlicker et al, 1992 Reiser &Hamprecht (1989) andEmerit et al (1993) and was recently confirmed in NIE-1 15 cells by Barann et al (1993 those found in other 5-HT3 receptor models. However, as already mentioned above, the disadvantage of this ionic condition was that stimulation with 5-HT had to be carried out in the presence of SP in order to obtain a reliably high ['4C]-guanidinium influx (Reiser & Hamprecht, 1989;Emerit et al, 1993;Barann et al, 1993).…”

“…In particular, anpirtoline inhibited the ['4C]-guanidinium influx, in NlE-1 15 neuroblastoma cells (Reiser et al, 1989;Emerit et al, 1993;Bonisch et al, 1993), the Bezold-Jarisch reflex in rats (Fozard, 1984;McQueen & Mir, 1989) and the cisplatin-induced emesis in the domestic pig (in this species, this represents a novel assay for evaluation of antiemetic drugs ;Szelenyi et al, 1994). The potency of anpirtoline in these test systems was less than that of zacopride, tropisetron, and ondansetron but higher than that of metoclopramide, and it was in a similar range to that of MDL 72222.…”

“…Cells were cultured in a humidified atmosphere containing 5% CO2 at 37°C in vent flasks (Nunc. 750 Reiser et al, 1989;Emerit et al, 1993). After termination of incubation (for details, see Bonisch et al, 1993), the cells were dissolved in 0.5 ml 0.1% Triton X-100 and the ['4C]-guanidinium content of this solution was determined by liquid scintillation counting.…”

“…Ketamine (Ketavet, Parke-Davis, Freiburg, Germany) and xylazine (Rompun, Bayer, Leverkusen, Germany) were used in their commercial form. (Reiser & Hamprecht, 1989;Emerit et al, 1993). However, this response was potentiated by substance P (SP), 10 AM, which given alone caused only negligible…”

“…[I4C]-guanidinium influx (Reiser & Hamprecht, 1989;Emerit et al, 1993 . This response was resistant to tetrodotoxin but susceptible to blockade by 5-HT3 receptor antagonists at concentrations higher than those required in experiments with buffer A or in experiments on other 5-HT3 receptor models Anpirtoline, zacopride, tropisetron and MDL 72222, given alone did not cause a change in heart rate.…”