Study 6

TITLE

Potassium channel conductance: a mechanism affecting hair growth both in vitro and in vivo.

AUTHOR
Buhl AE; Waldon DJ; Conrad SJ; Mulholland MJ; Shull KL; Kubicek MF; Johnson GA; Brunden MN; Stefanski KJ; Stehle RG; et al

ORGANISATION
Dermatology Research, Upjohn Company, Kalamazoo, Michigan 49001.

SOURCE
J Invest Dermatol 1992 Mar; 98 (3): 315-9

LANGUAGE OF PUBLICATION
English

ABSTRACT
The opening of intracellular potassium channels has been suggested as a mechanism regulating hair growth. Enhancing the flux of potassium ions is a mechanism shared by several structurally diverse antihypertensive agents including minoxidil sulfate (the active metabolite of minoxidil), pinacidil, P-1075 (a potent pinacidil analog), RP-49,356, diazoxide, cromakalim, and nicorandil. Of these drugs, minoxidil, pinacidil, and diazoxide have been reported to elicit hypertrichosis in humans. This potassium channel hypothesis was examined by testing these drugs for effects on hair growth both in vitro and in vivo. For the in vitro studies, mouse vibrissae follicles were cultured for 3 d with drug and the effects on hair growth were measured by metabolic labeling. All drugs, except diazoxide, enhanced cysteine incorporation into the hair shafts of the cultured vibrissae. Diazoxide was poorly soluble and thus was tested only at low doses. Minoxidil, P-1075, cromakalim, and RP-49,356 were also evaluated in vivo by measuring hair growth effects in balding stumptail macaque monkeys. The drugs were administered topically to defined sites on balding scalps once per day for 4-5 months and the amount of hair grown was determined by monthly measurements of shaved hair weight. Three of the drugs produced significant increases in hair weight whereas, the RP-49,356 had no effect. These studies provide correlative evidence that the opening of potassium channels is an important regulatory mechanism for hair growth. This provides the impetus for further studies on this potentially important mechanism affecting hair biology. (AUTHOR)

MJTR: Hair GD. Potassium Channels PH.

MNTR: Animal. Benzopyrans PD. Cells, Cultured. Mice. Mice, Inbred C3H. Mice, Inbred C57BL. Minoxidil PD. Pyrroles PD. JOURNAL ARTICLE

RNUM: 0 (Benzopyrans); 0 (Pyrroles); 38304-91-5 (Minoxidil); 94470-67-4 (Cromakalim)

GEOT: UNITED STATES

IDEN: ISSN: 0022-202X. JOURNAL-CODE: IHZ. ENTRY-DATE: 920415. JOURNAL-SUBSET: M X. IM-DATE: 9206.

ACCE: 92185253