1 Thapsigargin (TPG, 3 mM) and cyclopiazonic acid (CPA, 10 mM) slowly increased muscle tone in the guinea-pig isolated tracheal muscle. A large sustained contraction was produced when 2.4 mM Ca 2+ was readmitted after 10 min exposure to Ca 2+ -free solution following 30 min treatment with TPG or CPA. 2 The sustained contraction after Ca 2+ readmission was partially inhibited by nifedipine (3 mM) and highly dependent on external Ca 2+. The TPG-and CPA-induced sustained contractions were 75% and 67%, respectively, of the sustained contraction produced by carbachol (Cch, 1 mM, EC 80 ) in the presence of nifedipine. 3 The contractions produced by Cch, TPG and CPA were all inhibited by isoprenaline (ISO) and sodium nitroprusside (SNP). In the presence of nifedipine, the IC 50 of ISO was 11, 17, and 23 nM and that of SNP was 0.5, 1, 0.8 mM for Cch-, TPG-, and CPA-induced contractions, respectively. The contraction produced by 60 mM K + was only weakly inhibited by ISO and SNP. As with ISO and SNP, the Cch-, TPG-and CPA-induced contractions were also similarly inhibited by SKF 96365 (100 mM) and cadmium (Cd 2+ , 100 mM). 4 It was concluded that TPG and CPA increased Ca 2+ in¯ux probably via a mechanism activated by Ca 2+ depletion of the sarcoplasmic reticulum. The susceptibility of the contraction produced by TPG, CPA and Cch to inhibition by ISO and SNP and also by SKF-96365 and Cd 2+ suggests that the contractions use common pathways for increasing intracellular Ca 2+, and that the contractions produced by K + involve a dierent mechanism.

Abstract1. In smooth muscles isolated from the guinea-pig trachea, the effects of dihydropyr idines, nifedipine and nicardipine on contractions produced by carbachol (Cch) were studied in normal (6mM) and excess K+ concentration (60mM