Physiology and pathophysiology of proteinase-activated receptors (PARs): proteinases as hormone-like signal messengers: PARs and more.

Proteinases like thrombin and trypsin, long known for their ability to activate the coagulation cascade or to act as digestive enzymes for many protein targets, are now recognized as hormone-like regulators of cell function. These serine proteinases activate cell signaling by triggering a novel family of G-protein-coupled receptors, termed proteinase-activated receptors (PARs). This article summarizes the unique mechanisms involved in PAR activation and outlines the many different settings in which the PARs act to regulate tissue function. The PARs can be seen to play a role in inflammatory processes in large part via a neurogenic mechanism. Apart from activating PARs to cause their physiological effects in tissues, proteinases can also mediate cell signaling via a number of other mechanisms, including the activation of growth factor receptors, like the one for insulin. Thus, this article also points out the non-PAR mechanisms whereby proteinases can have hormone-like actions in cells and tissues.