Enhancement of Fetal Rat Limb Bone Resorption by Phorbol Ester (PMA) and Ionophore A-23187

Overview

Journal Calcif Tissue Int

Specialty Pathology

Date 1988 Mar 1

PMID 3130168

Citations 3

Authors

D C Abraham

C L Wadkins

H H Conaway

Affiliations

Soon will be listed here.

Abstract

The present investigation was undertaken to determine if an interaction affecting 45Ca release from prelabeled fetal rat long bones could be elicited by the Ca2+ ionophore, A-23187, and the phorbol ester, 12-myristate 13-acetate (PMA). Treatment with either A-23187 at a concentration of 0.3 microM or PMA at concentrations of 10(-6) M, 10(-7) M, and 10(-8) M produced significant 45Ca mobilization. When A-23187 and PMA were combined, enhanced 45Ca release was observed on days 1 and 2 of culture. The stimulation of calcium mobilization noted on day 1 occurred when neither ionophore nor 10(-6) M PMA treatments alone produced significant 45Ca release. On day 2, cumulative 45Ca release elicited by the combination of A-23187 plus 10(-6) M PMA was slightly more than additive (15.9% for combination treatment vs. 13.7% for the sum of the individual treatments). Moreover, when A-23187 was combined with 10(-7) M PMA on day 2, an enhancement of 45Ca release was observed which was clearly more than additive (14.5% for combination treatment vs. 8.8% for the individual treatments), suggesting the possibility of a synergistic interaction between the two agents. These results were in marked contrast to those obtained with the inactive phorbol ester analog, phorbol 13-monoacetate. No stimulation of 45Ca release was observed with 10(-6) M and 10(-7) M phorbol 13-monoacetate alone nor was enhanced 45Ca release noted when the analog was combined with 0.3 microM A-23187.(ABSTRACT TRUNCATED AT 250 WORDS)

Citing Articles

Diacylglycerol Kinase ζ (DGKζ) Is a Critical Regulator of Bone Homeostasis Via Modulation of c-Fos Levels in Osteoclasts.

Zamani A, Decker C, Cremasco V, Hughes L, Novack D, Faccio R J Bone Miner Res. 2015; 30(10):1852-63.

PMID: 25891971 PMC: 4580562. DOI: 10.1002/jbmr.2533.

Adenyl cyclase and interleukin 6 are downstream effectors of parathyroid hormone resulting in stimulation of bone resorption.

Greenfield E, Shaw S, Gornik S, Banks M J Clin Invest. 1995; 96(3):1238-44.

PMID: 7657797 PMC: 185744. DOI: 10.1172/JCI118157.

[Influence of an activator of protein kinase C (TPA) and a calcium-mobilizing agonist (A 23187) on zinc metabolism in the rat].

Kramer K, Markwitan A, MONTIGEL C, Pallauf J Z Ernahrungswiss. 1992; 31(4):246-57.

PMID: 1492428 DOI: 10.1007/BF01610073.

References

Rappaport M, Stern P . Parathyroid hormone and calcitonin modify inositol phospholipid metabolism in fetal rat limb bones. J Bone Miner Res. 1986; 1(2):173-9. DOI: 10.1002/jbmr.5650010202. View

Halenda S, Zavoico G, Feinstein M . Phorbol esters and oleoyl acetoyl glycerol enhance release of arachidonic acid in platelets stimulated by Ca2+ ionophore A23187. J Biol Chem. 1985; 260(23):12484-91. View

Vicentini L, Villereal M . Activation of Na+/H+ exchange in cultured fibroblasts: synergism and antagonism between phorbol ester, Ca2+ ionophore, and growth factors. Proc Natl Acad Sci U S A. 1985; 82(23):8053-6. PMC: 391440. DOI: 10.1073/pnas.82.23.8053. View

HOKIN L . Receptors and phosphoinositide-generated second messengers. Annu Rev Biochem. 1985; 54:205-35. DOI: 10.1146/annurev.bi.54.070185.001225. View

May Jr W, Sahyoun N, Wolf M, Cuatrecasas P . Role of intracellular calcium mobilization in the regulation of protein kinase C-mediated membrane processes. Nature. 1985; 317(6037):549-51. DOI: 10.1038/317549a0. View

Dziak R, Stern P . Parathyromimetic effects of the ionophore, A23187, on bone cells and organ cultures. Biochem Biophys Res Commun. 1975; 65(4):1343-9. DOI: 10.1016/s0006-291x(75)80377-9. View

Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, NISHIZUKA Y . Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982; 257(13):7847-51. View

Weiel J, Adams D, Hamilton T . Biochemical models of gamma-interferon action: altered expression of transferrin receptors on murine peritoneal macrophages after treatment in vitro with PMA or A23187. J Immunol. 1985; 134(1):293-8. View

Truneh A, Albert F, Golstein P . Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Nature. 1985; 313(6000):318-20. DOI: 10.1038/313318a0. View

10.

Rasmussen H . The calcium messenger system (1). N Engl J Med. 1986; 314(17):1094-101. DOI: 10.1056/NEJM198604243141707. View

11.

Wolf M, LeVine 3rd H, May Jr W, Cuatrecasas P, Sahyoun N . A model for intracellular translocation of protein kinase C involving synergism between Ca2+ and phorbol esters. Nature. 1985; 317(6037):546-9. DOI: 10.1038/317546a0. View

12.

TASHJIAN Jr A, Ivey J, Delclos B, Levine L . Stimulation of prostaglandin production in bone by phorbol diesters and melittin. Prostaglandins. 1978; 16(2):221-32. DOI: 10.1016/0090-6980(78)90023-0. View

13.

Kaibuchi K, Takai Y, Sawamura M, Hoshijima M, Fujikura T, NISHIZUKA Y . Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation. J Biol Chem. 1983; 258(11):6701-4. View

14.

White J, Huang C, Hill Jr J, Naccache P, Becker E, Shaafi R . Effect of phorbol 12-myristate 13-acetate and its analogue 4 alpha-phorbol 12,13-didecanoate on protein phosphorylation and lysosomal enzyme release in rabbit neutrophils. J Biol Chem. 1984; 259(13):8605-11. View

15.

Rasmussen H . The calcium messenger system (2). N Engl J Med. 1986; 314(18):1164-70. DOI: 10.1056/NEJM198605013141807. View

16.

Lorenzo J, Raisz L . Divalent cation ionophores stimulate resorption and inhibit DNA synthesis in cultured fetal rat bone. Science. 1981; 212(4499):1157-9. DOI: 10.1126/science.6785885. View

17.

Ivey J, Wright D, TASHJIAN Jr A . Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A. J Clin Invest. 1976; 58(6):1327-38. PMC: 333304. DOI: 10.1172/JCI108588. View

18.

Hishikawa R, Fukase M, Yamatani T, Kadowaki S, Fujita T . Phorbol ester stimulates calcitonin secretion synergistically with A23187, and additively with dibutyryl cyclic AMP in a rat C-cell line. Biochem Biophys Res Commun. 1985; 132(1):424-9. DOI: 10.1016/0006-291x(85)91039-3. View

19.

Dziak R, Stern P . Responses of fetal rat bone cells and bone organ cultures to the ionophore, A23187. Calcif Tissue Res. 1976; 22(2):137-47. DOI: 10.1007/BF02010353. View

20.

Conaway H, DIEZ L, Raisz L . Effects of prostacyclin and prostaglandin E1 (PGE1) on bone resorption in the presence and absence of parathyroid hormone. Calcif Tissue Int. 1986; 38(3):130-4. DOI: 10.1007/BF02556872. View