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Novel and established potassium channel openers stimulate hair growth in vitromodes of action in hair follicles.: implications for their

By Gareth C. Davies, M. Julie Thornton, Tracey J. Jenner, Yi-Ju Chen, J.B. Hansen, R.D. Carr and Valerie A. Randall

Abstract

NoAlthough 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

Topics: Bioassay, Diazoxide, Hair follicles, Glibenclamide, Minoxidil, NNC 55-0118, Organ culture, Phenol red, Tolbutamide
Year: 2005
DOI identifier: 10.1111/j.0022-202X.2005.23643.x
OAI identifier: oai:bradscholars.brad.ac.uk:10454/4017
Provided by: Bradford Scholars
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