Regulation of vascular endothelial cells and vascula smooth muscle cells by multiple P2Y receptor subtypes

Receptors for nucleotides regulate all aspects of vascular function. Here, the role and function of P2Y receptors in vascular endothelium and smooth m uscle cell proliferation are explored. in both cell types the presence of m ultiple P2Y receptors is commonplace; however, the identity and role of the se receptors is dependent on the vessel of origin. This is clearly seen wit h endothelial cells. The commonest observation is coexisting P2Y(1) and P2Y (2) (or P2Y(4)) receptors coupled through inositol 1,4,5-trisphosphate prod uction to Ca2+ mobilisation. However, in some endothelial cells other P2Y r eceptors are present. Brain microvascular endothelial cells, for example, e xhibit a variety of responses with profiles which cannot be fully explained by cloned P2Y receptors, and which are coupled to diverse receptor-effecto r mechanisms. These include p42/p44 mitogen-activated protein kinase activa tion, enhanced cyclic AMP synthesis and raised cytosolic Ca2+ in the absenc e of detectable rises in inositol 1,4,5-trisphosphate. These responses can be expected to influence endothelial prostacyclin and nitric oxide producti on, permeability, adhesion factor expression, and leukocyte-endothelial int eraction. P2Y receptors also regulate proliferative responses. Previously, data has been presented indicating that nucleotides acting on P2Y receptors can enhance cell proliferation in response to other agents. Here, we discu ss evidence that UTP is an antiproliferative regulator in human vascular sm ooth muscle cells and that P2Y(4) receptors may be involved in this respons e. (C) 2001 Wiley-Liss, Inc.