Role of the brain t-butylbicyclophosphorothionate receptor in vertebrate resistance to endrin, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane and cypermethrin.

Certain populations of mosquitofish (Gambusia affinis) are highly resistant to endrin (42-fold), but are not cross-resistant to cypermethrin. These populations show relatively low levels of resistance (2-fold) to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and t-butylbicyclophosphorothionate (TBPS). Studies comparing specific [35S]TBPS binding to brain membrane preparations from resistant and susceptible fish indicate a reduced binding capacity for TBPS in membranes from resistant fish. Endrin was about twice as potent in competitively inhibiting [35S] TBPS binding in vitro to membranes from susceptible fish as compared to membranes from resistant fish, suggesting that TBPS binding sites in resistant fish brain are less sensitive to endrin. Endrin was 37 times as potent in competitively inhibiting [35S]TBPS binding in vivo to membranes from susceptible fish compared to membranes from resistant fish, indicating that a contributory factor is involved in endrin resistance. Data for TBPS inhibition of [35S]TBPS binding revealed an approximate 2-fold difference between resistant and susceptible for both in vitro and in vivo IC50, indicating that an altered TBPS binding site is the only factor involved in TBPS resistance. DDT did not inhibit [35S] TBPS binding, suggesting that DDT resistance is not due to changes at the TBPS receptor. These data support the hypothesis that two factors operate in vertebrate resistance to endrin, whereas only one of these factors confers TBPS resistance. These resistance mechanisms are not functional against cypermethrin.