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 greater than Mn2+ greater than 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.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism*; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D008345:Manganese; D011813:Quinuclidinyl Benzilate; D009532:Nickel; D002217:Carbachol; D014700:Verapamil; D006152:Cyclic GMP; D002118:Calcium