Effect of some calcium antagonists on muscarinic receptor-mediated cyclic GMP formation

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. There 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.