Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin modifies the effects of PTH on osteoblast-like cells. However, the basis for this effect is unknown. In bone and kidney cells, the effects of PTH on cellular function are mediated by second messengers generated through both the phospholipase C and adenylate cyclase systems. Therefore, we examined the effects of insulin on PTH second messenger generation in UMR-106-01 rat osteoblastic osteosarcoma cells. PTH produced a rapid, transient increase in intracellular free calcium concentration ([Ca2+]i) which was maximal at 30 sec and was only minimally reduced in the absence of extracellular calcium. Inositol-triphosphate (IP3) production was increased in parallel. PTH stimulation of [Ca2+]i was concentration-dependent from 0.5-1,000 nM, with half-maximal stimulation at approximately 50 nM PTH. A 30-sec exposure to 50 nM PTH produced 32% and 23% increases in IP1 and IP3 production, respectively (both P less than 0.05). Although insulin alone did not significantly alter basal [Ca2+]i, a 1-min exposure to 1-100 nM insulin produced a concentration-dependent suppression of the PTH-stimulated transient increase in [Ca2+]i and IP3 generation. 100 nM insulin decreased 50 nM PTH stimulation of [Ca2+]i and IP3 levels by 84% (P less than 0.02) and 80% (P less than 0.001), respectively. Preexposure to insulin also decreased PTH stimulation of intracellular cAMP levels, but to a lesser degree. A 1-min exposure to 100 nM insulin produced a 32% (P less than 0.01) decrease in PTH-stimulated cAMP generation, but lower insulin concentrations were without significant effects. These results demonstrate that in UMR-106-01 cells, insulin suppresses PTH stimulation of second messengers generated through both the phospholipase C and adenylate cyclase systems, but has a more marked effect on the former.
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PMID:Insulin acutely suppresses parathyroid hormone second messenger generation in UMR-106-01 osteoblast-like cells: differential effects on phospholipase C and adenylate cyclase activation. 185 51

In previous studies, we have reported that PGF2alpha stimulates phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP-binding protein in osteoblast-like MC3T3-E1 cells, and that PGF2alpha and PGE1 induce interleukin-6 (IL-6) synthesis via activation of protein kinase C and protein kinase A, respectively. In the present study, we investigated the effect of tiludronate, a bisphosphonate known to inhibit bone resorption, on the PGF2alpha- and PGE1-induced IL-6 synthesis in these cells. Tiludronate significantly suppressed the PGF2alpha-induced IL-6 secretion in a dose-dependent manner in the range between 0.1 and 30 microM. However, the IL-6 secretion induced by PGE1 or (Bu)2cAMP was hardly affected by tiludronate. The choline formation induced by PGF2alpha was reduced by tiludronate dose-dependently in the range between 0.1 and 30 microM. On the contrary, tiludronate had no effect on PGF2alpha-induced formation of inositol phosphates. Tiludronate suppressed the choline formation induced by NaF, known as an activator of heterotrimeric GTP-binding protein. However, tiludronate had little effect on the formation of choline induced by TPA, a protein kinase C activator. Tiludronate significantly inhibited the NaF-induced IL-6 secretion in human osteoblastic osteosarcoma Saos-2 cells. These results strongly suggest that tiludronate inhibits PGF2alpha-induced IL-6 synthesis via suppression of phosphatidylcholine-hydrolyzing phospholipase D activation in osteoblasts, and that the inhibitory effect is exerted at the point between heterotrimeric GTP-binding protein and phospholipase D.
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PMID:Tiludronate inhibits interleukin-6 synthesis in osteoblasts: inhibition of phospholipase D activation in MC3T3-E1 cells. 958 64

Studies were undertaken to determine whether PTH-related protein (PTHrP) (107-139) mobilizes [Ca(2+)](i) in osteoblastic osteosarcoma UMR 106 cells. PTHrP (107-139), in a manner similar to PTHrP (107-111), induced a rapid [Ca(2+)](i) response in these cells that was dose dependent (EC(50) of approximately 0.1 pM) and more efficient than that of PTHrP (1-36) (EC(50) of approximately 1 nM). This effect of PTHrP (107-139) was abrogated by micromolar doses of verapamil or nifedipine. However, it was unaffected by 10 microM U73122 (a phospholipase C inhibitor), 100 microg/ml heparin (an inositol 1,4,5-trisphosphate receptor inhibitor), or 400 ng/ml pertussis toxin (a G(i) inhibitor), which inhibited the [Ca(2+)](i) response to PTHrP (1-36), or by either 25 nM bisindolylmaleimide I (BIM), a protein kinase (PK) C inhibitor, or 1 microM phorbol-12-myristate-13-acetate preincubation (22 h). PTHrP (107-139) and PTHrP (1-36), at 100 nM, desensitized the [Ca(2+)](i) response to a second challenge with the same peptide, but not with the other peptide in these cells. PTHrP (7-34), a type 1 PTH/PTHrP receptor (PTH1R) antagonist, decreased the effect of PTHrP (1-36) on [Ca(2+)](i). In contrast, PTHrP (107-111), but neither PTHrP (109-138) nor PTHrP (7-34), abolished this effect of PTHrP (107-139). Both PTHrP (107-139) and PTHrP (1-36), added together at submaximal doses, induced a higher [Ca(2+)](i) response. Moreover, PTHrP (107-139) increased the efficacy of PTHrP (1-36) on [Ca(2+)](i), but decreased its induced increase in PKA activity in these cells. Verapamil or nifedipine (at 50 microM) or 25 nM BIM, but not 25 microM adenosine 3',5'-cyclic monophosphorothioate, Rp-isomer, a PKA inhibitor, abolished the PTHrP (107-139)-induced increase in interleukin 6 messenger RNA (assessed by RT, followed by PCR) in UMR 106 cells. This peptide also increased c-fos messenger RNA in these cells; an effect inhibited by BIM, but unaffected by either verapamil or EGTA. These findings support the existence of high-affinity receptors for PTHrP (107-139), associated with an induced Ca(2+) influx, different from the PTH1R in UMR 106 cells. The present results suggest that PTHrP could affect bone turnover by interacting with the PTH1R and other yet unknown receptors in bone cells through complex mechanisms.
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PMID:C-terminal parathyroid hormone-related protein (PTHrP) (107-139) stimulates intracellular Ca(2+) through a receptor different from the type 1 PTH/PTHrP receptor in osteoblastic osteosarcoma UMR 106 cells. 1141 93