Detail of "86-88-4"

Reference

A role for serotonin in a-naphthylthiourea-induced pulmonary edema

A role for serotonin in a-naphthylthiourea-induced pulmonary edema. Mais, Dale E.; Bosin, Talmage R. (Sch. Med., Indiana Univ., Bloomington, IN 47405, USA). Toxicol. Appl. Pharmacol., 74(2), 185-94 (English) 1984. CODEN: TXAPA9. ISSN: 0041-008X. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 14 The role of 5-HT [50-67-9] in the pathophysiol. of a-naphthylthiourea (ANTU) [86-88-4]-induced pulmonary edema was examd. in mice. Mice treated with ANTU (10 mg/kg, i.p.) rapidly developed pulmonary edema which was maximal at 3 h and was resolved by 12 h. The lung content of both endogenous 5-HT and a tracer dose of 5-[3H]HT paralleled the time course of the development and resoln. of the pulmonary edema. ANTU produced thrombocytopenia (58-72%) at all time points, and an elevated platelet content of 5-HT and 5-[3H]HT during the resoln. phase (6-12 h). Drugs possessing select effects on 5-HT altered the edematogenic response to ANTU. Fluoxetine, a selective inhibitor of 5-HT uptake, potentiated the pulmonary edema, whereas clorgyline, an irreversible inhibitor of type A monoamine oxidase, was without effect. Reserpine which depletes 5-HT stores prevented both thrombocytopenia and pulmonary edema in response to ANTU. Reloading the lung and platelet 5-HT stores of reserpinized animals reestablished the normal response to ANTU. Pretreatment with the selective 5-HT2 receptor antagonist, ketanserin, prevented the thrombocytopenia, the increase in lung content of 5-HT and 5-[3H]HT, and prevented the edematogenic response to ANTU by 70%. These data indicate a major role for 5-HT in the pathophysiol. of acute lung microvascular injury produced by ANTU.

Potentiation of a-naphthylthiourea-induced lung injury by prostaglandin E1 and platelet depletion

Potentiation of a-naphthylthiourea-induced lung injury by prostaglandin E1 and platelet depletion. Fantone, J. C.; Kunkel, R. G.; Kinnes, D. A. (Med. Sch., Univ. Michigan, Ann Arbor, MI, USA). Lab. Invest., 50(6), 703-10 (English) 1984. CODEN: LAINAW. ISSN: 0023-6837. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) a-Naphthylthiourea (ANTU)(I) [86-88-4]produces lung injury in rats in a dose-dependent manner. The effects of prostaglandin E1 (PGE1) [745-65-3] on ANTU-induced lung injury were investigated. Systemic administration of 15-(S)-15-methyl-PGE1 (15-M-PGE1) [35700-26-6], a stable analog of PGE1, potentiated lung injury induced by ANTU in a dose- and time-dependent manner. 15-M-PGE1 (1 mg/kg, s.c.) administered 1 h prior to ANTU treatment (1 mg/kg, i.p.) resulted in a 164% increase in pleural effusion formation and a 42% increase in wet lung wt. at 4 h after ANTU administration. This was assocd. with increased pulmonary endothelial cell blebbing and gap formation with a decrease in the no. of platelet thrombi in 15-M-PGE1-treated animals compared with controls. 15-(S)-15-Methylprostaglandin F2a [35700-23-3] was less effective than 15-M-PGE1 in potentiating ANTU-induced lung injury. Platelet depletion, but not neutrophil depletion, also potentiated ANTU-induced lung injury, suggesting a protective role for platelets. Platelets isolated from 15-M-PGE1-treated animals demonstrated ~50% decreased aggregation response to ADP. 15-M-PGE1 (1 mg/kg) treatment combined with platelet depletion resulted in a 1.7-fold increase in pleural effusions in ANTU-treated (1 mg/kg) animals compared with platelet depletion alone. Thus, systemic treatment of rats with 15-M-PGE1 will potentiate ANTU-induced lung injury. This injury may be in part secondary to the ability of 15-M-PGE1 to inhibit platelet function. However, platelet depletion studies suggest that 15-M-PGE1 has addnl. effects, possibly on endothelial cells and/or vascular smooth muscle cells that contribute to the potentiation of ANTU-induced lung injury.