Modulation of carbachol-stimulated inositol phospholipid breakdown in rat cerebral cortical miniprisms by excitatory amino acids and by BAY K-8644 is dependent upon the assay calcium and potassium concentrations used.
The calcium and potassium ion dependency of the inositol phospholipid breakdown response to stimulatory agents has been investigated in rat cerebral cortical miniprisms. The calcium channel agonist BAY K-8644 (10 microM) potentiated the response to carbachol at 6 mM K+ when Ca2(+)-free, but not when 2.52 mM Ca2+ assay buffer was used. In Ca2(+)-free buffer, verapamil (10 microM) inhibited the response to carbachol at both 6 and 18 mM K+ but higher concentrations (30-300 microM) were needed when 2.52 mM Ca2+ was used. At these higher concentrations, however, verapamil inhibited the binding of 2 nM [3H]pirenzepine to muscarinic recognition sites. N-Methyl-D-Aspartate (NMDA, 100 microM) significantly reduced the basal phosphoinositide breakdown rate at 18 mM K+ at 1.3 mM Ca2+, but was without effect on the basal rate at other K+ and Ca2+ concentrations. In the presence of NMDA (100 microM) or quisqualate (100 microM), the responses to carbachol were reduced, the degree of reduction showing a complex dependency upon the assay K+ and Ca2+ concentrations used. These results indicate that the inositol phospholipid breakdown response to carbachol in cerebral cortical miniprisms can be modulated in a manner dependent upon the extracellular calcium and potassium concentrations used.
Tiger
G
G
Department of Pharmacology, University of Umeå, Sweden.
Fowler
C J
CJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009994:Osmolar Concentration; D010743:Phospholipids / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats
D000596:Amino Acids; D007295:Inositol Phosphates; D010743:Phospholipids; D016202:N-Methylaspartate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D016318:Quisqualic Acid; D002217:Carbachol; D011188:Potassium; D002118:Calcium