Developmental regulation of GABA(B) receptor function in rat spinal cord

GABA(B) receptors are heterodimers coupled to G-proteins. The present study was undertaken to investigate activation of GABA(B) receptors in cerebral cortex and spinal cord using [S-35]GTP gammaS binding assays, a direct meas ure of G-protein activity. The results revealed that the GABA(B) agonist ba clofen stimulates GTP gammaS binding in cerebral cortex, with an ED50 of 50 1 muM. This response is blocked by the GABA(B) receptor antagonist CGP 5584 5A (100nM). In contrast, baclofen-stimulated GTP gammaS binding was not obs erved in adult spinal cord tissue under similar incubation conditions, or a fter varying magnesium, calcium, GDP, [S-35]GTP gammaS, or membrane concent rations in the assay medium. Stimulation of adult rat spinal cord muscarini c receptors did result in a concentration-related increase in [S-35]GTP gam maS binding. Baclofen-stimulated GTP gammaS binding in adult spinal cord di d not appear after peripheral inflammation, despite significant increases i n GABA(B) subunit mRNA levels. As opposed to adult, appreciable GTP gammaS binding was observed in membranes prepared from spinal cords of rats within the first 14 days of postnatal development. suggesting that GABA(B) recept or function in the rat spinal cord is developmentally regulated. The result s indicate that GABA(B) receptors may not be coupled to G-proteins in the a dult rat spinal cord, or couple in a way that differs from that in newborns or adult cerebral cortex. (C) 2001 Elsevier Science Inc. All rights reserv ed.