Adrenomedullin has mitogenic effects on human oral keratinocytes: involvement of cyclic AMP

FEBS Letters

Farthing, Paula M¹  Brown, Dean W¹  Hagi-Pavli, Eleni¹  Kapas, Supriya¹ 

[1] Receptor Biology Group, Oral Diseases Research Centre, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Turner Street, London E1 2AD, UK

关键词: Adrenomedullin;    Oral keratinocyte;    Cyclic AMP;    Mitogenesis;    AM;    adrenomedullin;    CGRP;    calcitonin gene-related peptide;    cAMP;    cyclic adenosine monophosphate;    dbcAMP;    di-butyryl cAMP;    HUVEC;    human umbilical vein endothelial cells;    IBMX;    3-isobutyl-1-methylxanthine;    PBS;    phosphate buffered saline;    PKC;    protein kinase C;   

DOI  :  10.1016/S0014-5793(97)01384-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effects of the novel vasoactive regulatory peptide, adrenomedullin, on human oral keratinocytes was investigated. Adrenomedullin, acting via its specific receptor, stimulated a dose-dependent increase in DNA synthesis, and, in addition, stimulated further changes in the cell cycle resulting in the proliferation of keratinocytes. When cells were incubated in the presence of increasing concentrations of adrenomedullin, there was a rapid and dose-dependent rise in intracellular cyclic AMP levels. Stimulation of mitogenesis and cell proliferation in these cells were mimicked by the cell permeable cAMP analogue, di-butyryl cAMP. Adrenomedullin-stimulated mitogenesis was attenuated by the adenylyl cyclase inhibitor SQ22,536, but was unaffected by inhibitors of PKC, tyrosine kinase or the CGRP receptor antagonist, CGRP(8–37). These data identify adrenomedullin as a new mitogenic regulatory peptide of keratinocytes acting via the cAMP cascade.

【 授权许可】

Unknown