Effect of Some Calcium Antagonists on Muscarinic Receptor‐Mediated Cyclic GMP Formation

Abstract: Several calcium antagonists were screened for their effect on muscarinic acetylcholine receptor‐mediated cyclic GMP formation in murine neuroblastoma cells (clone N1E‐115). Mn²⁺, Ni²⁺, and verapamil rapidly antagonized the response noncompetitively, with the following order of potency: verapamil > Mn²⁺ > Ni²⁺. The effects of Mn²⁺ and Ni²⁺, but not those of verapamil, were largely reversed by increasing extracellular calcium concentration. Additional effects of these agents included displacement of [³H]quinuclidinyl benzilate binding by verapamil and elevation of cyclic GMP levels by Mn²⁺ and Ni²⁺ in the absence of agonists. These results are in support of the hypothesis that receptor‐mediated cyclic GMP formation by these cells is dependent upon entry of calcium into the cell and demonstrate the complexity of the effects of calcium antagonists.