ATP AND UTP ACTIVATE CALCIUM-MOBILIZING P-2U-LIKE RECEPTORS AND ACT SYNERGISTICALLY WITH INTERLEUKIN-1 TO STIMULATE PROSTAGLANDIN E-2 RELEASE FROM HUMAN RHEUMATOID SYNOVIAL-CELLS
Ga. Loredo et Hp. Benton, ATP AND UTP ACTIVATE CALCIUM-MOBILIZING P-2U-LIKE RECEPTORS AND ACT SYNERGISTICALLY WITH INTERLEUKIN-1 TO STIMULATE PROSTAGLANDIN E-2 RELEASE FROM HUMAN RHEUMATOID SYNOVIAL-CELLS, Arthritis and rheumatism, 41(2), 1998, pp. 246-255
Objective. To pharmacologically and functionally characterize calcium-
mobilizing purine receptors on adherent human rheumatoid synovial cell
s. Methods. Fura-2-loaded synovial cells were screened for changes in
cytosolic calcium concentration after the addition of purine receptor
agonists. Release of interleukin-1 (IL-1) and prostaglandin E-2 (PGE(2
)) was assessed by enzyme-linked immunosorbent assay (ELISA) and radio
immunoassay, respectively. The effect of IL-1 prestimulation on purine
-mediated PGE(2) release was determined. Results, ATP (1-100 mu M) and
UTP (1-100 mu M), but not 2-methylthio-ATP or adenosine, stimulated m
obilization of calcium from intracellular stores in synovial cells. AT
P and UTP stimulated a small. but significant, increase in PG release
from resting synoviocytes and a dramatic increase in PG release from s
ynoviocytes prestimulated with recombinant human IL-1 alpha. Neither A
TP nor UTP stimulated synoviocyte release of IL-1 as measured by speci
fic ELISA. The effects of ATP and UTP on PG secretion were mimicked by
phorbol 12-myristate 13-acetate and thapsigargin, and blocked by BAPT
A buffering of cytosolic calcium. Conclusion. Adherent human rheumatoi
d synovial cells mobilize intracellular calcium via a P-2U-like purine
receptor. P-2U receptor agonists stimulate PGE(2) release from synovi
ocytes, an effect that is greatly enhanced by IL-1 alpha prestimulatio
n and blocked by intracellular calcium buffering.