Effects of prostaglandin E2 and F2α on cytoplasmic pH in a clonal osteoblast‐like cell line, MOB 3–4

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Abstract
Prostaglandin E2 (PGE2, 5 ng/ml to 5 μg/ml) induced a dose‐dependent increase in cAMP accumulation, inositol phosphates (IPs) accumulation, and cytoplasmic free Ca2+ ([Ca2+]i) in a clonal osteoblast‐like cell line, MOB 3–4. In contrast, prostaglandin F2α (PGF2α, 5 ng/ml to 5 μg/ml) stimulated increases in IPs accumulation and [Ca2+]i without stimulating an increase in cAMP accumulation. Both PGE2 (>0.5 μg/ml) and PGF2α (≥0.5 μg/ml) increased cytoplasmic pH (pHi) from approximately 7.15 to 7.35 in BCECF‐loaded cells. A tumor promotor, phorbol 12‐myristate 13‐acetate (PMA, 0.1–100 nM) also increased pHi without effect on phosphoinositide hydrolysis. Both PGE2‐(5 μg/ml) and PMA‐ (100 nM) induced cytoplasmic alkalinization was inhibited by removal of extracellular Na+, or by pretreatment of the cells with amiloride (0.5 mM), an inhibitor of Na+/H+ exchange, or H‐7 (100 μM), a nonspecific inhibitor of protein kinase C. Thus, MOB 3–4 cells appeared to possess PGE2 receptors and PGF2α receptors: the former are coupled to adenylate cyclase and phospholipase C, and the latter are predominantly coupled to phospholipase C. Also the cells appeared to possess an amiloride‐sensitive Na+/H+ exchange activity, which increases pHi in response to PGE2 and PGF2α, as well as to PMA. Long‐term (48 hr) exposure of the cells to PGE2 at a high concentration (5 μg/ml), but not to PGF2α and PMA, decreased DNA synthesis in the serum‐deficient medium. Thus, cytoplasmic alkalinization appeared insufficient for cell replication. At least in MOB 3–4 cells, the inhibitory effect of PGE2 on DNA synthesis may be due to the cAMP messenger system.

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