Sulphate conjugation of minoxidil in rat skin.
Minoxidil sulphotransferase (MST) activity was determined in the cytosolic fraction of rat skin and liver. MST of rat skin is similar to the P (phenol)-form of phenosulphotransferase (PST) of human tissues with respect to thermostability and inhibition by 2,6-dichloro-4-nitrophenol (DCNP). p-Nitrophenol, a prototype substrate of human P-PST form, inhibits MST at micromolar concentration while millimolar concentrations of dopamine and tyramine, substrates of human M-(monoamine)-PST, are required to elicit a similar degree of inhibition. The enzymatic transfer of 35S from sodium 35sulphate to minoxidil was also demonstrated suggesting that the rat skin is potentially capable of synthesizing 3'-phosphoadenosine-5'-phosphosulphate (PAPS) from inorganic sulphate and utilizing it for the biosynthesis of minoxidil sulphate, its active metabolite. Thus, it is conceivable that the pharmacological action of minoxidil as a promoter of hair growth could be carried out by the cutaneous tissues without the contribution of hepatic or other extrahepatic organs.
Wong
K O
KO
Department of Biochemistry, Faculty of Medicine, National University of Singapore.
Tan
A Y
AY
Lim
B G
BG
Wong
K P
KP
D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D004795:Enzyme Stability; D006358:Hot Temperature; D008099:Liver / Q000201:enzymology; D008914:Minoxidil / Q000378:metabolism*; D009596:Nitrophenols / Q000494:pharmacology; D010724:Phosphoadenosine Phosphosulfate / Q000096:biosynthesis; D051381:Rats; D012867:Skin / Q000201:enzymology / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism; D014439:Tyramine / Q000494:pharmacology
D009596:Nitrophenols; D013431:Sulfates; D010724:Phosphoadenosine Phosphosulfate; D008914:Minoxidil; C015802:2,6-dichloro-4-nitrophenol; D015238:Sulfotransferases; C066827:minoxidil sulfotransferase; D004298:Dopamine; D014439:Tyramine; C024836:4-nitrophenol