title: Angiotensin II stimulates proliferation of primary human keratinocytes via a non-AT1, non-AT2 angiotensin receptor.
abstract: Angiotensin II is a hormone with long known cardiovascular actions. Recent studies revealed an additional role for angiotensin II in the regulation of cell proliferation. This study was performed to clarify whether skin is a target organ for these novel angiotensin actions. Radioligand binding studies identified a high-affinity angiotensin receptor on human primary keratinocytes in vitro with a Kd of 4.5 nM and a Bmax of 0.12 nM. Competition experiments with losartan and PD 123177 revealed that this receptor was not of the AT1- nor the AT2-subtype. Stimulation of human keratinocytes with angiotensin II (10(-10) to 10(-5) M) led to a dose dependent increase in 3H-thymidine incorporation, indicating that the keratinocyte receptor mediates a mitogenic effect. This effect is comparable at 10(-9) M to stimulation of keratinocytes by EGF (50ng/ml) and FGF (50ng/ml). These results demonstrate for the first time a possible physiological role for angiotensin II in human skin involving the regulation of keratinocyte proliferation.
authors.affiliation: Department of Dermatology, Virchow Klinikum, Humboldt Universität, Berlin, Germany.
authors.forename: U M
authors.initials: UM
authors.lastname: Steckelings
authors.forename: M
authors.initials: M
authors.lastname: Artuc
authors.forename: M
authors.initials: M
authors.lastname: Paul
authors.forename: M
authors.initials: M
authors.lastname: Stoll
authors.forename: B M
authors.initials: BM
authors.lastname: Henz
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D001667:Binding, Competitive; D002455:Cell Division; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects*; D008024:Ligands; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena
chemical_list: D008024:Ligands; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor