Specificity of methoctramine in blocking muscarinic receptors which inhibit adenylate cyclase in cerebellar granule cells.

In primary cultures of cerebellar granule cells, activation of muscarinic receptors stimulates both hydrolysis of phosphatidylinositol (PI) and inhibition of adenylate cyclase. The specificity of three muscarinic receptor antagonists, pirenzepine, methoctramine and (-)quinuclidinyl xanthene-9-carboxylate [(-)QNX], in blocking carbachol-stimulated hydrolysis of PI and inhibition of adenylate cyclase were determined. Pirenzepine was found to be nonspecific in blocking the carbachol-stimulated hydrolysis of PI and inhibition of adenylate cyclase, while methoctramine specifically antagonized carbachol-stimulated inhibition of adenylate cyclase with 600 times greater potency than carbachol-stimulated hydrolysis of PI.