The in vitro effect of toluene diisocyanate on lymphocyte cyclic adenosine monophosphate production by isoproterenol, prostaglandin, and histamine: a possible mode of action.
Toluene diisocyanate (TDI) significantly inhibits the rise in intracellular cyclic 3',5'-adenosine monophosphate (cAMP) that follows in vitro incubation of human lymphocytes with 6.7 x 10(-3) M isoproterenol and 1 x 10(-6) M prostagladin E1 (p less than 0.05). TDI has no significant effect on th production of lymphocyte cAMP following incubation with histamine (1 x 10(-3) M). The inhibitory action of TDI is greatest at a concentration of 3.3 x 10(-4) M and diminishes as the TDI concentration is increased or decreased. TDI also caused four- to fivefold stimulation of lymphocyte cAMP, an effect that is maximal at 1 x 10(-3) M, a concentration which has no significant inhibitory effect on stimulation of cAMP by isoproterenol or prostagladin E1. Conversely, 3.3 x 10(-4) M TDI, which inhibits cAMP production by isoproterenol and prostaglandin, has little stimulatory effect itself on cAMP production. This evidence suggests that TDI might induce obstructive airways disease through pharmacologic mechanisms and that TDI may be acting as a partial agonist.
D001249:Asthma / Q000139:chemically induced*; D003485:Cyanates / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors*; D008168:Lung / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D011458:Prostaglandins E / Q000037:antagonists & inhibitors*; D012997:Solvents; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage / Q000494:pharmacology*
D003485:Cyanates; D011458:Prostaglandins E; D012997:Solvents; D014051:Toluene 2,4-Diisocyanate; D006632:Histamine; D000242:Cyclic AMP; D007545:Isoproterenol; D004121:Dimethyl Sulfoxide