Interactions between phospholipase C-coupled and N-methyl-D-aspartate receptors in cultured cerebellar granule cells: protein kinase C mediated inhibition of N-methyl-D-aspartate responses.
The N-methyl-D-aspartate (NMDA) receptor of rat cerebellar granule cells in primary culture is inhibited by phospholipase C-coupled receptor activation. In the absence of ionotropic agonist, cells modulate their cytoplasmic free Ca2+, [Ca2+]c, in response to stimulation of M3 muscarinic receptors, metabotropic glutamate receptors, and endothelin receptors by the respective agonists carbachol, trans-1-amino-1,3-cyclopentanedicarboxylic acid, and endothelin-1. The response is consistent with the ability of phospholipase C-coupled receptors to release a pool of intracellular Ca2+ and induce a subsequent Ca2+ entry into the cell; both of these responses can be abolished by discharge of internal Ca2+ stores with low concentrations of ionomycin or thapsigargin. In the case of cells stimulated with NMDA, the [Ca2+]c response to the phospholipase C-coupled agonists is complex and agonist dependent; however, in the presence of ionomycin each agonist produces a partial inhibition of the NMDA component of the [Ca2+]c signal. This inhibition can be mimicked by the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate. It is concluded that NMDA receptors on cerebellar granule cells are inhibited by phospholipase C-coupled muscarinic M3, glutamatergic, and endothelin receptors via activation of protein kinase C.
Courtney
M J
MJ
Department of Biochemistry, University of Dundee, Scotland.
Nicholls
D G
DG
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D004347:Drug Interactions; D006098:Granulocytes / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008564:Membrane Potentials; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism* / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D016202:N-Methylaspartate; D011493:Protein Kinase C; D010738:Type C Phospholipases