The involvement of serotonin in the pneumotoxicity induced by N-methylthiobenzamide

N-Methylthiobenzamide (NMTB) and alpha-naphthylthiourea (ANTU) are pneumotoxicants which cause pulmonary edema and hydrothorax. Recently a role was assigned to serotonin (5-hydroxytryptamine, 5-HT) in the pneumotoxic response to ANTU (D.E. Mais and T.R. Bosin, 1984, Toxicol. Appl. Pharmacol. 74, 185-194). We therefore investigated the participation of 5-HT in NMTB-induced pneumotoxicity. Pulmonary clearance of 5-HT was studied after NMTB or ANTU using the rat isolated perfused lung. Lung 5-HT uptake was not depressed 5 hr after ANTU or NMTB, but was depressed 12 hr after compound administration. At both time points lungs were edematous as judged by lung wet weight to body weight ratios. Pretreatment with reserpine, a drug known to deplete 5-HT, did not affect the NMTB-induced decrease in lung 5-HT uptake, but did diminish the increased lung wet weight to dry weight ratios seen after NMTB administration in rats and mice and the increased lung wet weight to body weight ratios in mice. NMTB induces a dose-dependant increase in the incorporation of [14C]thymidine into mouse pulmonary DNA. This increase was attenuated, but not abolished, by pretreatment with reserpine. Reserpine did not alter survival time after NMTB or ANTU and did not shift the 14-day LD50 of NMTB. These data suggest that 5-HT is not a primary mediator in the pneumotoxic response to these thiono-containing compounds.