KINETICS OF TERT-[S-35]BUTYLBICYCLOPHOSPHOROTHIONATE BINDING IN THE CEREBRAL-CORTEX OF NEWBORN AND ADULT-RATS - EFFECTS OF GABA AND RECEPTOR DESENSITIZATION

The effects of GABA on the kinetics of tert[S-35]butylbicyclophosphoro thionate ([S-35]TBPS) binding to the convulsant site of GABA(A) recept ors were studied in membrane suspensions from the cerebral cortex of n ewborn (1-day-old) and adult (go-day-old) rats. TBPS dissociation was biphasic in neonates and adults, indicating that more than one interco nvertible state of [S-35]TBPS binding sites may be present in the cere bral cortex. In the absence of GABA, the fast (t(1/2), 11 min) and slo w (t(1/2), 77 min) components of TBPS dissociation in newborn rats wer e approximately fourfold slower than in adults, The acceleration of th e dissociation rates caused by 2 mu M GABA, however, was more robust i n neonates than in adults (six- to ninefold vs. twofold increase, resp ectively). Moreover, the dissociation rates of TBPS in membranes prein cubated with 2 mu M GABA (dissociation started by adding 40 mu M picro toxin) were two- to fourfold slower than in membranes preincubated wit hout GABA (dissociation started by adding 40 mu M picrotoxin plus 2 mu M GABA). Taken together, these results suggest that (1) the closed st ate of GABA(A) receptors is associated with a more effective steric ba rrier for the binding of TBPS in neonates compared with adults, (2) GA BA produces a larger acceleration of the binding kinetics of TBPS in n eonates than in adults, and (3) long incubations with GABA may cause r eceptor desensitization, which in turn slows down the dissociation rat es of TBPS.