Acid-sensing receptor found on RA, PsA synoviocytes

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Acid-sensing receptor found on RA, PsA synoviocytes



Nov 2, 2005



Janis

Galveston, TX - Inflammation often leads to low pH, and a newly

discovered cell receptor that responds to increased acidity might be

a major player in the process that turns the early inflammation of

diseases such as rheumatoid arthritis (RA) and psoriatic arthritis

(PsA) into lasting damage, according to Drs Burgess N Christensen,

Karin Westlund, and colleagues (University of Texas Medical Branch,

Galveston). In the September 2005 issue of American Journal of

Physiology-Cell Physiology, they describe a G-protein-coupled, acid-

sensing receptor found on synoviocytes that releases calcium in

response to low pH in joint fluids [1].

Westlund tells rheumawire that this receptor might be a key player in

the progression of early inflammation to joint destruction. " The

receptor will be activated when the synovial fluid pH falls below

6.8, with maximum cell responses at pH 6.4. This could occur when

lactic acid is built up [within the joint] with an early inflammatory

response, " Westlund says.

Receptor triggered by low pH in inflamed joint

Although other G-protein-coupled receptors (GPCRs) have been cloned

and described, Westlund says that none were previously known to exist

within the joint. Furthermore, all previously described acid-sensing

receptors are ion channels, not G-protein-coupled receptors.

" Furthermore, this receptor has different characteristics from the

other GPCRs described previously. Most notably, it is activated at a

lower pH, " Westlund says.





Under conditions of stress, other cellular processes are being shut

down, but this receptor is being turned on.





The result, Westlund explains, is that under conditions of stress,

other cellular processes are being shut down, but this receptor is

being turned on. " The receptor may provide a means for selective cell

metabolic events, allowing survival and allowing the cell to operate

under these adverse conditions, " she says.

The investigators found the new receptor on synoviocytes from primary

cultures, on synoviocytes from patients with RA, and on synoviocytes

from patients with psoriatic arthritis. Receptors from all of these

sites were proton-activated and mobilized intracellular calcium in

response to low pH. This calcium signal is suspected of playing a

role in downstream inflammatory and cellular proliferative responses

of synovial fibroblasts.

" An important question is whether these acid-evoked responses are

important in fibroblast-derived cells under normal physiological

conditions or, more particularly, in ischemic and inflammatory

conditions, where destructive and reperfusion processes regularly

occur—for example, in synovial and muscle tissues, " the authors write.





Other tissues without acid-sensing receptors like this may not do as

well in stress/low-oxygen/low-pH states.





If so, this receptor becomes an interesting therapeutic target.

" There might potential for altering cell-injury sequelae. However,

the receptor may need to be quelled to reduce symptomatology. There

may be time-sequence relevance and/or reperfusion relevance for

activation of this receptor in the joint, " Westlund says. " Other

tissues without acid-sensing receptors like this may not do as well

in stress/low-oxygen/low-pH states. Kidney, bone, joint, and muscle

tissues would be expected to have similar receptors, since they have

greater potential to experience this pH range, and, indeed, acid-

sensing receptors in some of these tissues have been reported in the

past 20 months. "



Source 

Christensen BN, Kochukov M, McNearney TA, et al. Proton-sensing G

protein-coupled receptor mobilizes calcium in human synovial cells.

Am J Physiol Cell Physiol 2005; 289:C601-C608.

http://www.jointandbone.org/viewArticle.do?primaryKey=589621