Abstract

A GREAT deal of effort has been expended, especially during the last decade, toward elucidation of the site and mechanism of action of mercurial diuretics. As a result of the contributions of many investigators,. several concepts have developed and are generally held. Histochemical studies dealing with renal protein-bound sulfhydryl groupsV and stopflow proceduresV indicate that the site of action is the proximal tubule. That the loop of Henle and collecting duct may participate cannot :be ruled out and, indeed, is actually implicated in the sulfhydryl stu’dies and also by the fact the mercurials interfere with potassium transport. Studies dealing with mechanism of action have centered around two focal points. The first involves the nature of the renal receptor and the second is concerned with the chemical nature of the reaction with receptor. A two-point receptor involving a sulfhydryl group has been suggested by Pitts et aZ.5 and by Mudge and Weiner6 but these investigators offer opposing views concerning the form of mercury which reacts with receptor. The dormer workers believe that mercury attaches by one valence to a point on the receptor. The second point of the receptor reacts with the organic fragment attached to the second valence of mercuric mercury; the latter have proposed that release of free mercuric io,n by fracture of a carbon-mercury bond, and subsequent attachment of divalent mercury to the double receptor are necessary for inhibition of sodium reabsorption. This conclusion is well-supported by their demonstrations that inorganic mercury attached to a suitable carrier seems to be more active than any organic compound, that acidotiis, which potentiates mercurial diuresis, speeds fracture of caribon-mercury bonds in vitro, and that stable mercury compounds are not diuretic. The work described Bin this report is an outigrowth of aI1 the valuable,

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