Prostaglandin E2 activates outwardly rectifying Cl(-) channels via a cAMP-dependent pathway and reduces cell motility in rat osteoclasts |
| |
Authors: | Okamoto Fujio Kajiya Hiroshi Fukushima Hidefumi Jimi Eijiro Okabe Koji |
| |
Institution: | Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan 814-0193. fujipi@college.fdcnet.ac.jp |
| |
Abstract: | We examined changes in electrical and morphological properties of rat osteoclasts in response to prostaglandin (PG)E2. PGE2 (>10 nM) stimulated an outwardly rectifying Cl current in a concentration-dependent manner and caused a long-lasting depolarization of cell membrane. This PGE2-induced Cl current was reversibly inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), and tamoxifen. The anion permeability sequence of this current was I > Br Cl > gluconate. When outwardly rectifying Cl current was induced by hyposmotic extracellular solution, no further stimulatory effect of PGE2 was seen. Forskolin and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) mimicked the effect of PGE2. The PGE2-induced Cl current was inhibited by pretreatment with guanosine 5'-O-2-(thiodiphosphate) (GDPS), Rp-adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS), N-(2-p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride (H-89), and protein kinase A inhibitors. Even in the absence of nonosteoclastic cells, PGE2 (1 µM) reduced cell surface area and suppressed motility of osteoclasts, and these effects were abolished by Rp-cAMPS or H-89. PGE2 is known to exert its effects through four subtypes of PGE receptors (EP1EP4). EP2 and EP4 agonists (ONO-AE1-259 and ONO-AE1-329, respectively), but not EP1 and EP3 agonists (ONO-DI-004 and ONO-AE-248, respectively), mimicked the electrical and morphological actions of PGE2 on osteoclasts. Our 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. prostanoid receptor agonists; electrophysiology; motile activity; bone resorption |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《American journal of physiology》浏览原始摘要信息 |
| 点击此处可从《American journal of physiology》下载免费的PDF全文 |
|