A COMPARATIVE-STUDY OF INHIBITION OF ACETYLCHOLINESTERASE, TRYPSIN, NEUROPATHY TARGET ESTERASE, AND SPLEEN-CELL ACTIVATION BY STRUCTURALLY RELATED ORGANOPHOSPHORUS COMPOUNDS

Organophosphorus (OF) compounds can bind to and inactivate several tar get molecules other than acetylcholinesterase (AChE). In the present s tudy, five sets of structurally related organophosphorus compounds wer e used to evaluate the relationships between organophosphorus binding sites of AChE, neuropathy target esterase (NTE), trypsin, and the targ et molecule(s) involved in inhibition of splenocyte activation by OP c ompounds. The concentration of each OP compound required to inhibit en zyme activity or splenocyte activation by concanavalin A by 50% was de termined. The pattern of IC50 values indicated that AChE, trypsin, NTE , and the molecule(s) involved in inhibition of splenocyte activation are distinct with regard to patterns of inhibition by OP compounds. Ho wever, there was a striking similarity in the patterns of inhibition f or trypsin and NTE with substantial differences for only 2 of 20 compo unds. This pattern suggests similarity in the active sites of these mo lecules. There were also similarities in the IC50 patterns for lymphoc yte activation and trypsin or NTE activity. However, the correlation w as not as strong as between NTE and trypsin, and the data suggested th e possibility of multiple target molecules for inhibition of splenocyt e activation by OP compounds. More importantly, there was essentially no correlation between the pattern of IC,, values for AChE and splenoc yte activation. This strongly suggests that acetylcholine and AChE of the type found in the brain are not important in the regulation of spl enocyte activation by concanavalin A.