Pharmacological properties of a new and potent calmodulin antagonist, HF2035

We previously represented that HF2035, a benzene-sulfonamide derivative with toluidine structure, inhibited the activity of rabbit neuronal nitric oxide synthase (cNOS). In this study, we examined the effects of HF2035 on endothelial NOS in a bioassay using vascular strips of rabbit carotid artery w...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1996, Vol.71 (suppl.1), p.166-166
Main Authors: Kato, Masumi, Saito, Nozomi, Hla Win, Nang Hla, Hidaka, Hiroyoshi
Format: Article
Language:eng ; jpn
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Summary:We previously represented that HF2035, a benzene-sulfonamide derivative with toluidine structure, inhibited the activity of rabbit neuronal nitric oxide synthase (cNOS). In this study, we examined the effects of HF2035 on endothelial NOS in a bioassay using vascular strips of rabbit carotid artery with and without endothelium. HF2035 inhibited acetylcholine- and calcium ionophore-induced relaxation of endothelium-intact strips with an ED50 of 1.5 μM and 2.8 μM, respectively. However, HF2035 did not inhibit an exogenous NO donor-induced relaxation of endothelium-denuded strips. HF2035 was unable to inhibit the activity of the inducible NOS in isolated thoracic aorta of rat treated with E. coli lipopolysaccharide. HF2035 inhibited the activity of recombinant rat nNOS with a Ki of 0.78 μM. Kinetic analysis indicated that this inhibitory effect of HF2035 was competitive with respect to calmodulin. HF2035 also inhibited calmodulin-dependent enzymes. These findings suggest that HF2035 is a new and potent calmodulin antagonist, possess a high membrane permeability.
ISSN:0021-5198
DOI:10.1016/S0021-5198(19)36905-7