Neurotensin stimulation of mast cell secretion is receptor-mediated, pertussis-toxin sensitive and requires activation of phospholipase C.

Pretreatment of isolated rat serosal mast cells with U-73122, an aminosteroid inhibitor of phospholipase C, inhibited histamine secretion in response to neurotensin (NT). This inhibition reached a maximum after 1 h of pretreatment at 37 degrees C and was dependent upon the concentration of U-73122 (IC50 approximately 0.2 microM). The inactive analog, U-73343, had no effect on the secretory response to NT. Pretreatment of mast cells with U-73122 also blocked histamine secretion in response to substance P (SP), mastoparan (MP), compound 48/80, or amidated NT (NT-NH2). Stimulation of mast cells by NT was accompanied by a rise in the level of intracellular free calcium and a rapid (within seconds) increase in the level of inositol trisphosphate (IP3) which was inhibited by pretreatment of the cells with U-73122. Pretreatment of isolated mast cells with pertussis toxin (PTx) blocked histamine release in response to NT as well as to all peptides tested. PTx had no effect on histamine secretion elicited by anti-IgE stimulation of sensitized mast cells. Pretreatment of mast cells with SR 48692, a NT-receptor antagonist, had no effect on histamine release induced by MP. At a high concentration (100 nM) SR 48692 partially inhibited the response to NT-NH2. These results, together with our earlier findings with SR 48692, indicate that the signal transduction pathway in mast cells activated by NT requires a specific NT-receptor, the activation of phospholipase C, and the involvement of a PTx sensitive G protein. The peptides SP and MP, and compound 48/80, while also requiring the activation of PLC and a PTx sensitive G protein, are not inhibited by the NT-R antagonist, SR 48692, suggesting that they exert their actions either via a different mast cell receptor or via a receptor-independent mechanism.

Negative pressure pulmonary edema after acute upper airway obstruction.

STUDY OBJECTIVES: To review the clinical characteristics and the pathogenesis of negative pressure pulmonary edema, and to determine its incidence in surgical patients. DESIGN: Retrospective case-report study. SETTING: Operating room, postanesthesia care unit and surgical intensive care of a teaching hospital. PATIENTS: 30 surgical adult ASA physical status I, II, III, IV, and V patients who suffered from negative pressure pulmonary edema during the period 1992-1995. MEASUREMENTS AND MAIN RESULTS: This study showed a rapid onset of negative pressure pulmonary edema after acute upper airway obstruction, due mainly to laryngospasm in the postoperative period and to upper airway pathology in the preoperative period. Negative pressure pulmonary edema appeared more frequent in healthy (ASA physical status I and II), middle-aged and male patients, with a general incidence of 0.094%. The resolution was relatively rapid after reestablishment of the airway, adequate oxygenation, and positive airway pressure application. The clinical course was uncomplicated in all the patients. CONCLUSIONS: In this study, negative pressure pulmonary edema presented a relatively high incidence. Prevention, early diagnosis, and prompt treatment allowed a rapid and uncomplicated resolution.