Beta2-adrenergic receptor antagonist accelerates skin barrier recovery and reduces epidermal hyperplasia induced by barrier disruption.
Effects of topical application of adrenergic receptor agonists and antagonists on epidermal barrier repair rate after barrier disruption were studied. Agonists and antagonists of beta1-adrenergic receptor did not affect the barrier repair rate. On the other hand, beta2-adrenergic receptor agonists, procaterol and alprenol, delayed barrier recovery and the beta2 receptor antagonist, ICI-118551, blocked the delay. Moreover, topical application of ICI-118551 or beta1,2 receptor antagonist, clenbuterol alone accelerated barrier recovery. Antagonists of alpha1 and alpha2 receptors did not affect barrier recovery. The delay of barrier repair induced by prodaterol hydrochloride was blocked by a voltage-gated calcium channel blocker, verapamil or nifedipine. In cultured human keratinocytes, procaterol increased the intracellular calcium concentration and the increase was blocked by ICI-118551 and also by verapamil or nifedipine. Topical application of ICI-118551 partially blocked the epidermal hyperplasia induced by acetone treatment under low environmental humidity. These results suggest that the beta2-adrenergic receptor is specifically associated with skin barrier homeostasis.
Denda
Mitsuhiro
M
Shiseido Research Center, Yokohama, Japan. mitsuhiro.denda@to.shiseido.co.jp
Fuziwara
Shigeyoshi
S
Inoue
Kaori
K
D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002976:Clenbuterol / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006813:Humidity; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009543:Nifedipine / Q000494:pharmacology; D017265:Procaterol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011412:Propanolamines; C026777:ICI 118551; D000526:Alprenolol; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium; D017265:Procaterol; D002976:Clenbuterol