The same enzymes catalyze sulfation of minoxidil, minoxidil analogs and catecholamines.
Rat liver sulfation of minoxidil and minoxidil analogs is described and the enzymes responsible are compared with those that sulfate catecholamines. Our study of minoxidil sulfation showed male-dominant sex dimorphism of the enzyme activity due to two enzymes that coelute with dopamine sulfotransferases. The most abundant isoform, in our routine assay, is minoxidil sulfotransferase 2 (P2). Sulfation ability by this enzyme parallels minoxidil analog antihypertensive ability. Minoxidil, analog and dopamine sulfotransferases were not separable by several different chromatographic methods, supporting their identity. The minoxidil sulfotransferase activity dropped in hypophysectomized males, due mostly to diminished levels of minoxidil sulfotransferase 2/dopamine sulfotransferase II, which appears to be aryl sulfotransferase IV. Its relationship to the minoxidil sulfotransferase reported by the Falany group is not clear. Here, we describe the exploration of rat liver sulfation of antihypertensive minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxide), and several minoxidil analogs. Minoxidil sulfation was first reported in rat and human liver cytosol by Johnson's group at Upjohn [1,2]. Our interest in the sulfation process arose because direct action of minoxidil sulfate had been implicated both in vivo [3,4] and in vitro [5] in blood pressure control processes.
Chemistry Department, University of Dayton, OH 45469.
S S
SS
Singer
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism; D015239:Arylsulfotransferase / Q000378:metabolism*; D002384:Catalysis; D002395:Catecholamines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007016:Hypophysectomy; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008914:Minoxidil / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D015238:Sulfotransferases / Q000378:metabolism*
D000959:Antihypertensive Agents; D002395:Catecholamines; D008914:Minoxidil; D015238:Sulfotransferases; C066827:minoxidil sulfotransferase; D015239:Arylsulfotransferase