Proteinase-Activated Receptors and Arthritis

Abstract

The novel family of proteinase-activated receptors (PARs) is activated through proteolytic cleavage by serine proteinases. This family of G proteincoupled receptors and their activating enzymes are found widely throughout the body. It has been known for some time that during arthritic conditions, high levels of serine proteinases are released from joint tissue and contribute to joint degradation. Expression of PARs is also enhanced in arthritic joints and act to mediate the intracellular signalling of the serine proteinases, leading to various inflammatory and painful effects. This chapter summarises what is known so far on all four of the currently known PARs with respect to their links with arthritis and discusses how these receptors may represent novel targets for the development of new arthritic treatments.

Osteoarthritis is a neurological disease – an hypothesis

“…Neuropeptides that have been shown to sensitize joint afferents include nociceptin [ 45 ], vasoactive intestinal peptide [ 42 ], substance P [ 46 ], and galanin [ 47 ]. Other inflammatory mediators that have been shown to reduce the firing threshold of joint mechanosensory afferents include prostaglandins [ 48 , 49 ], cytokines [ 50 ], serine proteases [ 51 ], and serotonin [ 52 ]. The mechanism by which these algesic molecules sensitize peripheral nerves is uncertain but is likely due to an alteration in the gating properties of nociceptor cation channels.…”