title: Novel and established potassium channel openers stimulate hair growth in vitro: implications for their modes of action in hair follicles.
abstract: Although ATP-sensitive potassium (K(ATP)) channel openers, e.g., minoxidil and diazoxide, can induce hair growth, their mechanisms require clarification. Improved drugs are needed clinically. but the absence of a good bioassay hampers research. K(ATP) channels from various tissues contain subtypes of the regulatory sulfonylurea receptor, SUR, and pore-forming, K(+) inward rectifier subunits, Kir6.X, giving differing sensitivities to regulators. Therefore, the in vitro effects of established potassium channel openers and inhibitors (tolbutamide and glibenclamide), plus a novel, selective Kir6.2/SUR1 opener, NNC 55-0118, were assessed on deer hair follicle growth in serum-free median without streptomycin. Minoxidil (0.1-100 microM, p<0.001), NNC 55-0118 (1 mM, p<0.01; 0.1, 10, 100 microM, p<0.001), and diazoxide (10 microM, p<0.01) increased growth. Tolbutamide (1 mM) inhibited growth (p<0.001) and abolished the effect of 10 microM minoxidil, diazoxide and NNC 55-0118; glibenclamide (10 microM) had no effect, but prevented stimulation by 10 microM minoxidil. Phenol red stimulated growth (p<0.001), but channel modulator responses remained unaltered. Thus, deer follicles offer a practical, ethically advantageous in vitro bioassay that reflects clinical responses in vivo. The results indicate direct actions of K(ATP) channel modulators within hair follicles via two types of channels, with SUR 1 and SUR 2, probably SUR2B, sulfonylurea receptors.
authors.affiliation: Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, UK.
authors.forename: Gareth C
authors.initials: GC
authors.lastname: Davies
authors.forename: M Julie
authors.initials: MJ
authors.lastname: Thornton
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Jenner
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: John B
authors.initials: JB
authors.lastname: Hansen
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carr
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Randall
mesh_terms: D000818:Animals; D004396:Coloring Agents; D003670:Deer; D003981:Diazoxide / Q000494:pharmacology; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008914:Minoxidil / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010637:Phenolsulfonphthalein; D015221:Potassium Channels / Q000502:physiology*; D014044:Tolbutamide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004396:Coloring Agents; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D008914:Minoxidil; D014044:Tolbutamide; D010637:Phenolsulfonphthalein; D003981:Diazoxide