Ontogenetic development of GABAB-receptor signaling cascade in plasma membranes isolated from rat brain cortex; The number of GABAB-receptors is high already shortly after the birth

摘要

Our data indicate the significant intrinsic efficacy of GABABreceptors in rat brain cortex already at birth (PD1, PD2). Subsequently, baclofen-and SKF97541-stimulated G-protein activity, measured by agonist-stimulated, high-affinity [~(35)S]GTP?S binding assay, was increased; the highest level of both baclofen and SKF97541-stimulated [~(35)S]GTP?S binding was detected between PD10 and PD15. In older rats, baclofen-and SKF97541-stimulated [35S]GTP?S binding was continuously decreased so, that the level in adult, 90-days old animals, was not different from that in newborn animals. The potency of G-protein response to baclofen (characterized by EC_(50) values) was also high at birth but unchanged by further postnatal development. An individual variance among different agonists was observed in this respect as the potency of SKF97541 response was decreased between the birth and adulthood. Accordingly, the highest plasma membrane density of GABA_B-R, determined by saturation binding assay with antagonist [~3H]CGP54626, was measured in 1-day old animals (2.27±0.08 pmol · mgmg~(-1)). The further development was reflected in a decrease of [3H]CGP54626 binding as the Bmax values of 1.38±0.05 and 0.93±0.04 pmol · mg~(-1) were determined in PM isolated from 13-and 90-days old rats, respectively.