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Davies GC, Thornton MJ, Jenner TJ, Chen YJ, Hansen JB, Carr RD, Randall VA: Novel and established potassium channel openers stimulate hair growth in vitro: implications for their modes of action in hair follicles. J Invest Dermatol. 2005 Apr;124(4):686-94.
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. |
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