Pharmacology of agents that affect calcium. Agonists and antagonists

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 sensitivie 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.