Effect of calmodulin antagonists on contraction and 45Ca movements in rat aorta.

To study the selectivity of calmodulin antagonists it was assumed that they should inhibit noradrenaline (NA)- and K(+)-induced contractions similarly without an accompanying inhibition of 45Ca uptake. Therefore, in isolated rat aorta the effects of W-7, calmidazolium and trifluoperazine on contraction and 45Ca uptake elicited by K+ and NA were investigated. Calmidazolium (10(-5)-10(-4) mol/l) elicited an incomplete inhibiton of K(+)- and NA-induced contraction and 45Ca uptake. Trifluoperazine inhibited the NA-induced contractions at lower concentrations (10(-8)-10(-6) mol/l) than the K(+)-induced contraction (10(-6)-10(-4) mol/l). The K(+)- and NA-induced 45Ca uptake was blocked by trifluoperazine (10(-5) mol/l). W-7 (10(-5)-10(-4) mol/l) inhibited the K(+)- and NA-induced contraction, however, in the same concentration range W-7 diminished the K(+)- and NA-induced 45Ca uptake. In conclusion, the results indicate that calmidazolium and trifluoperazine are hardly useful as calmodulin antagonists because of their additional properties, whereas W-7 seems to be the least unspecific of the calmodulin antagonists studies.