Role of protein sulfation in vasodilation induced by minoxidil sulfate, a K+ channel opener
Evidence from contractile, radioisotope ion flux and electrophysiological studies suggest that minoxidil sulfate (MNXS) acts as a K+ channel opener in vascular smooth muscle. This study was designed to examine possible biochemical mechanisms by which MNXS exerts such an effect. Experiments performed...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 258; no. 3; pp. 1091 - 1097 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.09.1991
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Subjects | |
Online Access | Get full text |
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Summary: | Evidence from contractile, radioisotope ion flux and electrophysiological studies suggest that minoxidil sulfate (MNXS) acts
as a K+ channel opener in vascular smooth muscle. This study was designed to examine possible biochemical mechanisms by which
MNXS exerts such an effect. Experiments performed in the isolated rabbit mesenteric artery (RMA) showed that MNXS, 5 microM,
but not the parent compound minoxidil, was a potent vasodilator. Whereas the relaxant effects of an another K+ channel opener
vasodilator, BRL-34915 (cromakalim), were removed by washing with physiological saline solution, the effects of MNXS persisted
after repeated washout attempts. Furthermore, after an initial exposure of segments of intact RMA to [35S] MNXS, greater than
30% of the radiolabel was retained 2 hr after removal of the drug. In contrast, retention of radiolabel was not detected with
either [3H]MNXS (label on the piperidine ring of MNXS) or [3H]minoxidil (each less than 3% after a 2-hr washout). These data
suggested that the sulfate moiety from MNXS was closely associated with the vascular tissue. To determine if proteins were
the acceptors of sulfate from MNXS, intact RMAs were incubated with [35S]MNXS, and then 35S-labeled proteins were separated
by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by fluorography. Preferential labeling of a 116
kD protein was detected by 2 and 5 min of treatment. A 43 kD protein (resembling actin) also showed significant labeling.
A similar profile of 35S-labeled proteins was observed in [35S] MNXS-treated A7r5 rat aortic smooth muscle cells, suggesting
that the majority of proteins labeled by [35S]MNXS in intact RMA were components of smooth muscle cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 None |
ISSN: | 0022-3565 1521-0103 |