Angiotensin II stimulates proliferation of primary human keratinocytes via a non-AT(1), non-AT(2) angiotensin receptor

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 nhl and a B-max of 0.12 nM. Competition experiments with losartan and PD 123177 revealed that this receptor was not of the AT(1)- nor the AT(2)-subtype. Stimulation of human keratinocytes with angiotensin II (10(-10) to 10(-9) M) led to a dose dependent increase in H-3-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. (C) 1996 Academic Press, Inc.