Metabotropic receptors for gamma-aminobutyric acid (GABA-B-R) play a crucial role in the regulation of synaptic transmission in the central nervous system (CNS). We study the ability of GABA-B-R to activate inhibitory G proteins in the rat brain.

In this context, we also analyze the changes of GABA-B receptor-initiated signaling cascade in the course of the ontogenetic development of CNS. Our results demonstrated that GABA-B receptors are present in the frontal rat brain cortex in large amount already at birth and their number gradually decreases during the ontogenetic development thus the content of GABA-B-R in the brain of adult animals is 2.5 times lower than in new born rats (Fig.1). The highest level of GABA-B-R-induced activity of cognate G proteins was detected at postnatal days 14 and 15 (Fig.2).

Ontogenetic profile of GABA-B receptors is in striking contrast to the general trend of the brain development which was monitored by the determination of Na,K– ATPase. The amount of this enzyme was systematically increased during the ontogenetic development thus the content of Na,K– ATPase in adult animals was 3 times higher than after the birth. (For further information please see publications Kagan et al. 2012; Dlouhá et al. 2013 and PhD thesis of D. Kagan, 2015.)

Obr. 1. Saturation of [³H]CGP54626 binding sites in brain cortex plasma membranes isolated from  1-,  13-  and  90-day-old  rats.

Obr. 2. Baclofen– and SKF97541–stimulated [³⁵S]GTPγS binding

Difference between agonist–stimulated and basal level of binding in brain cortex plasma membranes indicates the sharp maximum at PD15 and PD14.