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

Abstract

The calcium and potassium ion dependencyof the inositol phospholipid breakdown response to stimulatory agents has been investigated in rat cerebral cortical miniprisms. The calcium channel agonist BAY K-8644 (10 μM) potentiated the response to carbachol at 6 mM K + when Ca 2+-free, but not when 2.52 mM Ca 2+ assay buffer was used. In Ca 2+-free buffer, verapamil (10 μM) inhibited the response to carbachol at both 6 and 18 mM K +, but higher concentrations (30–300 μM) were needed when 2.52 mM Ca 2+ 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 μM) significantly reduced the basal phosphoinositide breakdown rate at 18 mM K + at 1.3 mM Ca 2+, but was without effect on the basal rate at other K + and Ca 2+ concentrations. In the presence of NMDA (100 μM) or quisqualate (100 μM), the responses to carbachol were reduced, the degree of reduction showing a complex dependency upon the assay K + and Ca 2+ 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.