Magnesium sulfate inhibits capacitative Ca^2+ of airway smooth muscle

• Published in: Japanese Journal of Pharmacology 1998, Vol.76 (suppl.2), p.297-297
• Main Authors: Hidekazu Setoguchi, Hayashi Yoshimura, Katsuya Hirano, Junji Nishimura, Hideo Kanaide
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Magnesium sulfate (MgSO_4 ) inhibits Ca^2+ and induces relaxation of airway smooth muscle (ASM). We have previously shown that MgSO_4 decreases intracellular Ca^2+ concentration ([Ca^2+ ]_i ) and tension induced by high K^+ depolarization or carbachol by inhibiting voltage dependent or receptor-operated Ca^2+ respectively. Recently, another Ca^2+ pathway, "capacitative Ca^2+ entry" has been introduced as a mechanism for the agonist-induced Ca^2+ The present study was designed to determine the effects of MgSO_4 on the capacitative Ca^2+ by using front-surface fluorometry of the fura-2-loaded porcine ASM strips. After recording the 100% response levels of [Ca^2+ ]_i and tension by the depolarization with 40 mM K^+ PSS, 10^-6 M thapsigargin, an inhibitor of sarcoplasmic reticulum Ca^2+ was applied in normal PSS. Thapsigargin induced a slow rise in [Ca^2+ ]_i , which reached a steady state level after 10 min without any tension development. This steady state increase in [Ca^2+ ]_i due to capacitative Ca^2+ was then maintained for at least 40 min of observation. The cumulative application of MgSO_4 during this period induced decreases in [Ca^2+ ]_i , in a concentration-dependent manner. The extent of inhibition in thapsigargin-induced increases in [Ca^2+ ]_i was smaller than that to carbachol-induced one. IC_50 values were 19.4 mM and 8.32 mM, respectively. It is concluded that MgSO_4 also inhibits capacitative Ca^2+ of the porcine ASM. The difference in potency for MgSO_4 to inhibit between thapsigargin- and carbachol-induced increases in [Ca^2+ ]_i may suggest that capacitative Ca^2+ alone can not explain all the agonist-induced Ca^2+ in ASM.