Beta2-adrenergic receptor agonist inhibits keratinocyte proliferation by mechanisms involving nitric oxide

Abstract

Introduction

Beta2-adrenoceptors regulate proliferation of keratinocytes. Nitric oxide (NO) produced by keratinocytes through stimulation of nitric oxide synthase (NOS) mediates keratinocyte proliferation. Aim: In this study, the mechanism interaction β-ARs and NO production on keratinocyte will be explored, and the important for proliferation will be studied.

Material and methods

To understand the relationship among β2-adrenoceptors, NO production and proliferation in keratinocytes, the experiment is divided to two parts. In the first part of the experiment, keratinocytes are divided into five groups which are treated with 0 M, 10 ^–7 M, 10 ^–6 M, 5 × 10 ^–6 M and 10 ^–5 M isoproterenol, respectively. In the second part of the experiment, the keratinocytes are divided into five groups which are treated with 10 ^–5 M isoproterenol and L-NMMA at doses of 0 M, 10 ^–6 M, 5 × 10 ^–6 M, 10 ^–5 M and 5 × 10 ^–5 M, respectively. We examine NOS expression, NO production, c-AMP level and proliferation in human keratinocytes.

Results

The results show that isoproterenol results in iNOS and ncNOS protein raised and the elevation of nitric oxide. L-NMMA can block the increase of iNOS and ncNOS protein expression and the ability to inhibit proliferation caused by isoproterenol.

Conclusions

Beta2-adrenergic receptor agonist mediates nitric oxide synthase to affect keratinocyte proliferation in skin. The physiological and pathological relationship of these discoveries remains to be defined. These results can provide new possibilities in the therapy of integumentary disease conditions linked with the dysfunction of β-AR-mediated NO production.