G protein-coupled receptors as potential drug targets for lymphangiogenesis and lymphatic vascular diseases.
G protein-coupled receptors (GPCRs) are widely expressed cell surface receptors that have been successfully exploited for the treatment of a variety of human diseases. Recent studies in genetically engineered mouse models have led to the identification of several GPCRs important for lymphatic vascular development and function. The adrenomedullin receptor, which consists of an oligomer between calcitonin receptor-like receptor and receptor activity modifying protein 2, is required for normal lymphatic vascular development and regulates lymphatic capillary permeability in mice. Numerous studies also suggest that lysophospholipid receptors are involved in the development of lymphatic vessels and lymphatic endothelial cell permeability. Given our current lack of pharmacological targets for the treatment of lymphatic vascular diseases like lymphedema, the continued identification and study of GPCRs in lymphatic endothelial cells may eventually lead to major breakthroughs and new pharmacological strategies for the treatment of lymphedema.
Dunworth
William P
WP
Department of Cell and Molecular Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Caron
Kathleen M
KM
D000818:Animals; D058286:Calcitonin Receptor-Like Protein; D004729:Endothelium, Lymphatic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects / Q000502:physiology*; D008209:Lymphedema / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D018003:Receptors, Calcitonin / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology; D049312:Receptors, Lysophospholipid / Q000502:physiology
C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; C545579:Calcrl protein, mouse; D018003:Receptors, Calcitonin; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid