Abstract
We examined effects of prostaglandin E2 (PGE2) on electrical and morphological properties of rat osteoclasts. PGE2 (>10 nM) stimulated an outwardly rectifying Cl− current and caused a long-lasting depolarization of cell membrane. This PGE2-induced Cl− current was reversibly inhibited by DIDS, NPPB and tamoxifen. The anion permeability sequence of this current was I−>Br−>=Cl−>gluconate−. When the Cl− current was induced by hyposmotic extracellular solution, no further stimulatory effect of PGE2 was observed. Forskolin and dibutyryl-cAMP mimicked the effect of PGE2. The PGE2-induced Cl− current was inhibited by pretreatment with GDPβS, Rp-cAMPS and H89. PGE2 (1 μM) also reduced cell surface area and suppressed motility of osteoclasts, and these effects were inhibited by Rp-cAMPS or H89. PGE2 is known to exert its effects through four subtypes of PGE receptors (EP1, EP2, EP3 and EP4). The EP2 (ONO-AE1-259) and EP4 (ONO-AE1-329) agonists, but not EP1 (ONO-DI-004) and EP3 (ONO-AE-248) agonists mimicked the electrical and morphological effcts of PGE2 on osteoclasts. These results show that PGE2 stimulates rat osteoclast Cl− current by activation of a cAMP-dependent pathway through EP2 and, to a lesser degree, EP4 receptors and reduces osteoclast motility. This effect is likely to reduce bone resorption. [Jpn J Physiol 54 Suppl:S131 (2004)]
