[Studies on desensitization of GABAB receptor coupled adenylate cyclase].
After preincubation of crude synaptic membranes (P2 membranes) with phorber ester (PMA) or GABAB receptor agonist baclofen (BAL), the rate of inhibition of BAL on basal adenylate cyclase (AC) activity and forskolin-stimulated AC activity significantly reduced (desensitized). This effect of BAL did not change after preincubation with forskolin suggesting that the desensitization mechanism of GABAB receptor coupled AC is related with activation of protein kinase C (PKC), but not with protein kinase A. It was further found that the equilibrium dissociation constant (Kd) of GABAB receptor was increased during desensitization. Our results suggest that PKC activation may cause some structural or conformational changes of GABAB receptor, resulting in an uncoupling from G protein and desensitization of GABAB receptor-coupled AC.
Yu
Z F
ZF
State Key Laboratory of Medical Neurobiology, Shanghai Medical University.
Cheng
G J
GJ
Hu
B R
BR
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001665:Binding Sites / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism
D018755:GABA Agonists; D018080:Receptors, GABA-B; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D001418:Baclofen