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 [35S]GTPgammaS binding assays, a direct measure of G-protein activity. The results revealed that the GABA(B) agonist baclofen stimulates GTPgammaS binding in cerebral cortex, with an ED50 of 50microM. This response is blocked by the GABA(B) receptor antagonist CGP 55845A (100nM). In contrast, baclofen-stimulated GTPgammaS binding was not observed in adult spinal cord tissue under similar incubation conditions, or after varying magnesium, calcium, GDP, [35S]GTPgammaS, or membrane concentrations in the assay medium. Stimulation of adult rat spinal cord muscarinic receptors did result in a concentration-related increase in [35S]GTPgammaS binding. Baclofen-stimulated GTPgammaS binding in adult spinal cord did not appear after peripheral inflammation, despite significant increases in GABA(B) subunit mRNA levels. As opposed to adult, appreciable GTPgammaS binding was observed in membranes prepared from spinal cords of rats within the first 14 days of postnatal development, suggesting that GABA(B) receptor function in the rat spinal cord is developmentally regulated. The results indicate that GABA(B) receptors may not be coupled to G-proteins in the adult rat spinal cord, or couple in a way that differs from that in newborns or adult cerebral cortex.
Moran
J M
JM
Department of Pharmacology, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Enna
S J
SJ
McCarson
K E
KE
D000367:Age Factors; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018080:Receptors, GABA-B / Q000096:biosynthesis* / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013462:Sulfur Radioisotopes
D018755:GABA Agonists; D018756:GABA Antagonists; D018727:Muscarinic Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D012333:RNA, Messenger; D018080:Receptors, GABA-B; D013462:Sulfur Radioisotopes; D006153:Guanosine Diphosphate; C085075:CGP 55845A; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010095:Oxotremorine; D001418:Baclofen; D008274:Magnesium; D002118:Calcium