KINETICS OF TERT-[S-35]BUTYLBICYCLOPHOSPHOROTHIONATE BINDING IN THE CEREBRAL-CORTEX OF NEWBORN AND ADULT-RATS - EFFECTS OF GABA AND RECEPTOR DESENSITIZATION
O. Giorgi et al., KINETICS OF TERT-[S-35]BUTYLBICYCLOPHOSPHOROTHIONATE BINDING IN THE CEREBRAL-CORTEX OF NEWBORN AND ADULT-RATS - EFFECTS OF GABA AND RECEPTOR DESENSITIZATION, Journal of neurochemistry, 67(1), 1996, pp. 423-429
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.