Novel and established potassium channel openers stimulate hair growth in vitro:: Implications for their modes of action in hair follicles

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:124

Article

Davies, GC ; Thornton, MJ ; Jenner, TJ ; Chen, YJ ; Hansen, JB ; Carr, RD ; Randall, VA

关键词: bioassay;    diazoxide;    glibenclamide;    minoxidil;    NNC 55-0118;    organ culture;    phenol red;    tolbutamide;   

DOI  :  10.1111/j.0022-202X.2005.23643.x

来源: Elsevier

【 摘 要 】

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 mu M, p < 0.001), NNC 55-0118 (1 mM, p < 0.01; 0.1, 10, 100 mu M, p < 0.001), and diazoxide (10 mu M, p < 0.01) increased growth. Tolbutamide (1 mM) inhibited growth (p < 0.001) and abolished the effect of 10 mu M minoxidil, diazoxide and NNC 55-0118; glibenclamide (10 mu M) had no effect, but prevented stimulation by 10 mu M 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.

【 授权许可】

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