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

J Neurochem. 1992 Sep;59(3):983-92. doi: 10.1111/j.1471-4159.1992.tb08339.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / metabolism*
  • Drug Interactions
  • Granulocytes / metabolism*
  • Ionomycin / pharmacology
  • Membrane Potentials
  • N-Methylaspartate / antagonists & inhibitors*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Protein Kinase C / physiology*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Type C Phospholipases / metabolism*

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Phorbol 12,13-Dibutyrate
  • Ionomycin
  • N-Methylaspartate
  • Protein Kinase C
  • Type C Phospholipases