Pharmacology of Agents that Affect Calcium

Agonists and Antagonists

¹ From the Department of Biochemical Pharmacology, State University of New York, Buffalo

Calcium utilization by smooth muscle is briefly reviewed. A variety of stimulant-evoked calcium mobilization processes exist including utilization of intracellular Ca²⁺ and translocation of Ca²⁺ through voltage-sensitive and insensitive channels. The extent of use of these several sources is both stimulant and tissue-dependent and it is probable that most smooth muscle excitation-contraction coupling processes employ more than a single Ca²⁺ source. A large number of agents have been described as "Ca²⁺-antagonists" and ideally there would exist antagonists specific for each mobilization process. This does not appear to be the case and the structural diversity of the many antagonists is consistent with multiple modes of action. Prominent among the Ca²⁺ antagonists are agents as verapamil, D600 and nifedipine which have as one component of their action inhibition of voltage sensitive Ca²⁺ channels. However, the mechanisms by which these agents act are unknown and it is also clear that they have important effects at sites other than Ca²⁺ channels.