ADRENOMEDULLIN HAS MITOGENIC EFFECTS ON HUMAN ORAL KERATINOCYTES - INVOLVEMENT OF CYCLIC-AMP

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 DN A 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 adrenomedul lin, there was a rapid and dose-dependent rise in intracellular cyclic AMP levels, Stimulation of mitogenesis and cell proliferation in thes e cells mere mimicked by the cell permeable cAMP analogue, dibutyryl c AMP, Adrenomedullin-stimulated mitogenesis was attenuated by the adeny lyl cyclase inhibitor SQ22,536, but was unaffected by inhibitors of PK C, 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. (C) 1997 Federation of Euro pean Biochemical Societies.