TY - JOUR
T1 - Sulfation of minoxidil by multiple human cytosolic sulfotransferases
AU - Anderson, Robert J.
AU - Kudlacek, Patrick E.
AU - Clemens, Dahn L.
N1 - Funding Information:
We thank Gar Johnson, Ph.D., who, while with the Upjohn Company, contributed to these studies, and Christopher Huerter, M.D., for doing the scalp skin biopsies; Richard Weinshilboum, M.D. and Diane Otterness for the generous gifts of the human liver TL PST, DHEA ST and EST cDNAs; Christine Halgard for her assistance with these studies; and the Upjohn Company for providing the minoxidil and minoxidil sulfate. This work was supported by the VA Medical Research Service (RJA, DLC), Nebraska Biomedical Research Association (RJA), Creighton University (RJA) and by grants from the Fraternal Order of Eagles (RJA) and The Upjohn Company (RJA).
PY - 1998/2/20
Y1 - 1998/2/20
N2 - Minoxidil is an antihypertensive agent and hair growth promoter that is metabolized by suffation to the active compound, minoxidil sulfate. Thermostable phenol sulfotransferase (TS PST or P-PST) was initially thought to catalyze the reaction, and the enzyme was designated minoxidil sulfotransferase (MNX-ST). Information about human ST activities toward minoxidil would be useful in developing the capacity to predict individual responses to minoxidil based on tissue levels of STs. Therefore, human STs were studied from platelet homogenates, partially purified platelets, scalp skin high speed supernatants and COS-I cell eDNA expressed preparations using a radiochemical enzymatic assay with minoxidil as the substrate. Studies showed the presence of TS PST, TL (thermolabile) PST and MNX-ST activities in human scalp skin. Biochemical properties and correlation studies suggested that in addition to TS PST, the TL PST activity, another ST activity or both were involved in the reaction. Partially purified human platelet TL PST tested with minoxidil and dopamine showed identical thermal stabilities and similar responses to the inhibitors 2,6-dichloro-nitrophenol (DCNP) and NaCl. To characterize the activity of TL PST toward minoxidil, several biochemical properties of the enzyme expressed from a human liver eDNA clone were investigated. When assayed with minoxidil and dopamine, thermal stabilities of the expressed enzyme were identical and IC50 values for the inhibitors DCNP and NaCl were similar. It was also demonstrated that eDNA encoded human liver dehydroepiandrosterone sulfotransferase and estrogen sulfotransferase contributed to the sulfation of minoxidil. The results confirm that at least four human STs contribute to minoxidil sulfation. MNX-ST activity represents a combination of ST activities. The data indicate that multiple ST activities should be taken into account in attempts to predict the regulation of minoxidil sulfation and individual responses to minoxidil.
AB - Minoxidil is an antihypertensive agent and hair growth promoter that is metabolized by suffation to the active compound, minoxidil sulfate. Thermostable phenol sulfotransferase (TS PST or P-PST) was initially thought to catalyze the reaction, and the enzyme was designated minoxidil sulfotransferase (MNX-ST). Information about human ST activities toward minoxidil would be useful in developing the capacity to predict individual responses to minoxidil based on tissue levels of STs. Therefore, human STs were studied from platelet homogenates, partially purified platelets, scalp skin high speed supernatants and COS-I cell eDNA expressed preparations using a radiochemical enzymatic assay with minoxidil as the substrate. Studies showed the presence of TS PST, TL (thermolabile) PST and MNX-ST activities in human scalp skin. Biochemical properties and correlation studies suggested that in addition to TS PST, the TL PST activity, another ST activity or both were involved in the reaction. Partially purified human platelet TL PST tested with minoxidil and dopamine showed identical thermal stabilities and similar responses to the inhibitors 2,6-dichloro-nitrophenol (DCNP) and NaCl. To characterize the activity of TL PST toward minoxidil, several biochemical properties of the enzyme expressed from a human liver eDNA clone were investigated. When assayed with minoxidil and dopamine, thermal stabilities of the expressed enzyme were identical and IC50 values for the inhibitors DCNP and NaCl were similar. It was also demonstrated that eDNA encoded human liver dehydroepiandrosterone sulfotransferase and estrogen sulfotransferase contributed to the sulfation of minoxidil. The results confirm that at least four human STs contribute to minoxidil sulfation. MNX-ST activity represents a combination of ST activities. The data indicate that multiple ST activities should be taken into account in attempts to predict the regulation of minoxidil sulfation and individual responses to minoxidil.
KW - Human skin sulfotransferases
KW - Minoxidil
KW - Recombinant sulfotransferases
KW - Sulfation
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U2 - 10.1016/S0009-2797(97)00120-8
DO - 10.1016/S0009-2797(97)00120-8
M3 - Article
C2 - 9566733
AN - SCOPUS:0032549060
SN - 0009-2797
VL - 109
SP - 53
EP - 67
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 1-3
ER -