Effects of various calmodulin antagonists on contraction of rabbit aortic strips.

Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), chlorpromazine, prenylamine and N2-dansyl-L-arginine-4-t-butylpiperidine amide on vascular smooth muscle contraction were compared by using helically cut strips of rabbit aorta. These compounds are reported to be calmodulin antagonists, in vitro. W-7 at a concentration of 1 x 10(-4) M significantly antagonized the contractile responses of aortic strips to the same extent as seen with norepinephrine, serotonin, histamine, prostaglandin F2 alpha, angiotensin II and KCl. On the other hand, the addition of 1 x 10(-4) M N-(6 aminohexyl)-1-naphthalenesulfonamide, an analog of W-7 which has no chloride molecule in the structure and possesses a lower affinity for calmodulin than W-7, did not antagonize aortic contractions. Chlorpromazine at a concentration of 1 x 10(-6) M specifically antagonized the norepinephrine-, serotonin- and histamine-induced contractions, but did not antagonize the prostaglandin F2 alpha-and angiotensin II-induced contractions. Inhibition of prenylamine of the contractile response of aortic strips to KCl was marked compared with the inhibition by this drug of the responses to other agonists. N2-dansyl-L-arginine-4-t-butylpiperidine amide selectively antagonized the serotonin- and KCl-induced contractions at a concentration of 1 x 10(-5) M, however, at this concentration, the responses to norepinephrine, histamine and prostaglandin F2 alpha were not affected by the drug. Thus, each calmodulin antagonist tested has a different spectrum of action and of these only W-7 has a specific interaction with calmodulin.