Characterization of Endothelin-Binding Sites in Human Skin and their Regulation in Primary Raynaud's Phenomenon and Systemic Sclerosis

Abstract

Endothelin (ET), which mediates vasoconstrictor and vasodilator activities via multiple receptor subtypes, has been implicated in the control of blood flow and vascular tone in human skin, and possibly in the abnormal vasoconstrictor response in primary Raynaud's phenomenon and systemic sclerosis. Using in vitro autoradiography we have examined the endothelin-binding characteristics and receptor subtypes of human skin, and sought to provide evidence for endothelin receptor regulation in skin from patients with primary or secondary Raynaud's phenomenon. Specific 125I-ET-1 and 125I-ET-3 binding sites were localized to microvessels of the sub-epidermal plexus and dermal papillae, larger blood vessels, sweat glands, epidermis, and hair follicles. Both ETA and ETB receptors were demonstrated in microvessels and other structures. ET receptor heterogeneity in skin vasculature suggests a role for ET as an autocrine/paracrine regulator of vasoconstrictor and vasodilator pathways in human skin. The presence of binding sites in epidermis and hair follicles suggests a possible mitogenic function for endothelin in human skin. Endothelin-binding density was significantly higher (p < 0.05) in microvessels of skin from patients with systemic sclerosis but not significantly different in Raynaud's phenomenon patients, compared to controls. Lack of down regulation of ET receptors in Raynaud's phenomenon and systemic sclerosis may contribute to the pathogenesis of vasospasm in these diseases.