Metabotropic glutamate receptor mGlu2 is resistant to homologous agonist-induced desensitization but undergoes protein kinase C-mediated heterologous desensitization.
To investigate the susceptibility of the group II metabotropic glutamate receptor mGlu2 to agonist-induced desensitization, the receptor was stably expressed in Chinese hamster ovary (CHO-mGlu2) or C6 glioma cells (C6-mGlu2). Exposure of CHO-mGlu2 cells to the group II mGlu receptor agonist (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (LCCG-1; 10 μM) for up to 15 h did not affect the subsequent ability of LCCG-1 to inhibit forskolin-stimulated cAMP accumulation. Similarly, in C6-mGlu2 cells, prolonged exposure to LCCG-1 also did not affect the subsequent ability of LCCG-1 to inhibit cAMP formation. In contrast, exposure of CHO-mGlu2 cells to the protein kinase C activator phorbol myristate acetate (PMA) suppressed the ability of LCCG-1 to inhibit cAMP formation. Using an in vitro model of group II mGlu receptor activity, the hemisected neonatal rat spinal cord preparation, the ability of the selective group II agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC) to depress the fast component of the dorsal root-evoked ventral root potential (fDR-VRP) did not desensitize when applied for up to 2 h. Together these results indicate that in contrast to most G protein-coupled receptors, the mGlu2 receptor is resistant to agonist-induced homologous desensitization, and that in vitro data suggests that resistance to desensitization is a physiologically relevant property of this mGlu receptor subtype.
Lennon
Siân M
SM
Department of Physiology and Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Rivero
Guadalupe
G
Matharu
Annelise
A
Howson
Patrick A
PA
Jane
David E
DE
Roberts
Peter J
PJ
Kelly
Eamonn
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000600:Amino Acids, Dicarboxylic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology
D000600:Amino Acids, Dicarboxylic; D020536:Enzyme Activators; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C035261:(alpha-carboxycyclopropyl)glycine; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases