Effect of Protriptyline on [Ca^(2+)]i and Viability in MDCK Renal Tubular Cells

10.4077/CJP.2017.BAF459

He-Hsiung Cheng；Chiang-Ting Chou；Wei-Zhe Liang；Chun-Chi Kuo；Pochuen Shieh；Jue-Long Wang；Chung-Ren Jan

Ca^(2+) ； MDCK cells ； protriptyline ； renal tubular cells

The Chinese Journal of Physiology

60卷2期（2017 / 04 / 30）

114 - 123

英文

Protriptyline has been used as an antidepressant. Clinically it has been prescribed in the auxiliary treatment of cancer patients. However, its effect on Ca^(2+) signaling and related physiology is unknown in renal cells. This study examined the effect of protriptyline on cytosolic free Ca^(2+) concentrations ([Ca^(2+)]i) and viability in Madin-Darby canine kidney (MDCK) tubular cells. Protriptyline induced [Ca^(2+)]i rises concentration-dependently. The response was reduced by 20% by removing extracellular Ca^(2+). Protriptyline-induced Ca^(2+) entry was not altered by protein kinase C (PKC) activity but was inhibited by 20% by three modulators of store-operated Ca^(2+) channels: nifedipine, econazole and SKF96365. In Ca^(2+)-free medium, treatment with the endoplasmic reticulum Ca^(2+) pump inhibitor 2,5- di-tert-butylhydroquinone (BHQ) or thapsigargin partially inhibited protriptyline-evoked [Ca^(2+)]i rises. Conversely, treatment with protriptyline inhibited partially BHQ or thapsigargin-evoked [Ca^(2+)]i rises. Inhibition of phospholipase C (PLC) with U73122 did not change protriptyline-induced [Ca^(2+)]i rises. Protriptyline at 5-200 μM decreased cell viability, which was not reversed by pretreatment with the Ca^(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/ AM). Together, in MDCK cells, protriptyline induced [Ca^(2+)]i rises by evoking PLC-independent Ca^(2+) release from the endoplasmic reticulum and other unknown stores, and Ca^(2+) entry via PKC-insensitive store-operated Ca^(2+) entry. Protriptyline also caused Ca^(2+)-independent cell death.

1. Chang, H.T.,Chou, C.T.,Liang, W.Z.,Lu, T.,Kuo, D.H.,Shieh, P.,Ho, C.M.,Jan, C.R.(2014).Effects of thymol on Ca2+ homeostasis and apoptosis in MDCK renal tubular cells.Chinese J. Physiol.,57,90-98.
   連結：
2. Chen, W.C.,Cheng, H.H.,Huang, C.J.,Lu, Y.C.,Chen, I.S.,Liu, S.I.,Hsu, S.S.,Chang, H.T.,Huang, J.K.,Chen, J.S.,Jan, C.R.(2007).The carcinogen safrole increases intracellular free Ca2+ levels and causes death in MDCK cells.Chinese J. Physiol.,50,34-40.
   連結：
3. Shieh, P.,Tsai, M.L.,Chiu, M.H.,Chen, Y.O.,Yi, N.L.,Jan, C.R.(2010).Independent effects of the broccoli-derived compound sulforaphane on Ca2+ influx and apoptosis in Madin-Darby canine renal tubular cells.Chinese J. Physiol.,53,215-222.
   連結：
4. Amsterdam, J.,Brunswick, D.,Mendels, J.(1980).The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels.Am. J. Psychiatry,137,653-662.
5. Biggs, J.T.,Ziegler, V.E.(1977).Protriptyline plasma levels and antidepressant response.Clin. Pharmacol. Ther.,22,269-273.
6. Bootman, M.D.,Berridge, M.J.,Roderick, H.L.(2002).Calcium signalling: more messengers, more channels, more complexity.Curr. Biol.,12,R563-R565.
7. Bozic, M.,Valdivielso, J.M.(2012).Calcium signaling in renal tubular cells.Adv. Exp. Med. Biol.,740,933-944.
8. Bynagari-Settipalli, Y.S.,Lakhani, P.,Jin, J.,Bhavaraju, K.,Rico, M.C.,Kim, S.,Woulfe, D.,Kunapuli, S.P.(2012).Protein kinase C isoform ε negatively regulates ADP-induced calcium mobilization and thromboxane generation in platelets.Arterioscler. Thromb. Vasc. Biol.,32,1211-1219.
9. Chang, H.T.,Chou, C.T.,Yu, C.C.,Tsai, J.Y.,Sun, T.K.,Liang, W.Z.,Lin, K.L.,Tseng, H.W.,Kuo, C.C.,Chen, F.A.,Kuo, D.H.,Pan, C.C.,Ho, C.M.,Shieh, P.,Jan, C.R.(2015).The mechanism of protriptyline-induced Ca2+ movement and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.J. Recept. Signal Transduct. Res.,35,429-434.
10. Clapham, D.E.(1995).Intracellular calcium. Replenishing the stores.Nature,375,634-635.
11. Davis, F.M.,Goulding, E.H.,D'Agostin, D.M.,Janardhan, K.S.,Cummings, C.A.,Bird, G.S.,Eddy, E.M.,Putney, J.W.(2016).Male infertility in mice lacking the store-operated Ca2+ channel Orai1.Cell Calcium,59,189-197.
12. Fang, Y.C.,Chou, C.T.,Chi, C.C.,Lin, K.L.,Li, Y.D.,Cheng, H.H.,Lu, Y.C.,Cheng, J.S.,Kuo, C.C.,Jan, C.R.(2013).Effect of diindolylmethane on Ca2+ homeostasis and viability in MDCK renal tubular cells.Hum. Exp. Toxicol.,32,344-353.
13. Florenzano, F.,Viscomi, M.T.,Mercaldo, V.,Longone, P.,Bernardi, G.,Bagni, C.(2006).P2X2R purinergic receptor subunit mRNA and protein are expressed by all hypothalamic hypocretin/orexin neurons.J. Com. Neurol.,498,58-67.
14. Greenblatt, D.J.,Koch-Weser, J.,Shader, R.I.(1974).Multiple complications and death following protriptyline overdose.JAMA,229,556-557.
15. Grynkiewicz, G.,Poenie, M.,Tsien, R.Y.(1985).A new generation of Ca2+ indicators with greatly improved fluorescence properties.J. Biol. Chem.,260,3440-3450.
16. Guse, A.H.(2015).Calcium mobilizing second messengers derived from NAD.Biochim. Biophys. Acta,1854,1132-1137.
17. Higgins, S.C.,Pilkington, G.J.(2010).The in vitro effects of tricyclic drugs and dexamethasone on cellular respiration of malignant glioma.Anticancer Res.,30,391-397.
18. Ishikawa, J.,Ohga, K.,Yoshino, T.,Takezawa, R.,Ichikawa, A.,Kubota, H.,Yamada, T.(2009).A pyrazole derivative, YM-58483, potently inhibits store-operated sustained Ca2+ influx and IL-2 production in T lymphocytes.J. Immunol.,170,4441-4449.
19. Jiang, N.,Zhang, Z.M.,Liu, L.,Zhang, C.,Zhang, Y.L.,Zhang, Z.C.(2006).Effects of Ca2+ channel blockers on store-operated Ca2+ channel currents of Kupffer cells after hepatic ischemia/reperfusion injury in rats.World J. Gastroenterol.,12,4694-4698.
20. Jo, S.H.,Hong, H.K.,Chong, S.H.,Choe, H.(2008).Protriptyline block of the human ether-à-go-go-related gene (HERG) K+ channel.Life Sci.,82,331-340.
21. Klimecka, M.,Szczegielniak, J.,Godecka, L.,Lewandowska-Gnatowska, E.,Dobrowolska, G.,Muszyńska, G.(2011).Regulation of wound-responsive calcium-dependent protein kinase from maize (ZmCPK11) by phosphatidic acid.Acta Biochim. Pol.,58,589-595.
22. Kohler, M.,Bloch, K.E.,Stradling, J.R.(2009).Pharmacological approaches to the treatment of obstructive sleep apnoea.Expert Opin. Investig. Drugs,18,647-656.
23. Korobkova, E.A.,Ng, W.,Venkatratnam, A.,Williams, A.K.,Nizamova, M.,Azar, N.(2010).In vitro studies of DNA damage caused by tricyclic antidepressants: a role of peroxidase in the side effects of the drugs.Chem. Res. Toxicol.,23,1497-1503.
24. Liu, C.P.,Chou, C.T.,Liang, W.Z.,Cheng, J.S.,Chang, H.T.,Kuo, D.H.,Ko, K.C.,Chiang, N.N.,Wu, R.F.,Shieh, P.,Jan, C.R.(2013).Pathways of [Ca2+]i rise evoked by angiotensin II in MDCK renal tubular cells.J. Recept. Signal Transduct. Res.,33,380-386.
25. Ma, J.,Luo, A.,Wu, L.,Wan, W.,Zhang, P.,Ren, Z.,Zhang, S.,Qian, C.,Shryock, J.C.,Belardinelli, L.(2012).Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes.Am. J. Physiol. Cell Physiol.,302,C1141-C1151.
26. Merritt, J.E.,Jacob, R.,Hallam, T.J.(1989).Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils.J. Biol. Chem.,264,1522-1527.
27. Mukherjee, S.,Trice, J.,Shinde, P.,Willis, R.E.,Pressley, T.A.,Perez-Zoghbi, J.F.(2013).Ca2+ oscillations, Ca2+ sensitization, and contraction activated by protein kinase C in small airway smooth muscle.J. Gen. Physiol.,141,165-178.
28. Nicotera, T.M.,Schuster, D.P.,Bourhim, M.,Chadha, K.,Klaich, G.,Corral, D.A.(2009).Regulation of PSA secretion and survival signaling by calcium-independent phopholipase A2β in prostate cancer cells.Prostate,69,1270-1280.
29. Peluso, J.J.,Pappalardo, A.,Fernandez, G.(2001).Basic fibroblast growth factor maintains calcium homeostasis and granulosa cell viability by stimulating calcium efflux via a PKC delta-dependent pathway.Endocrinology,142,4203-4211.
30. Quinn, T.,Molloy, M.,Smyth, A.,Baird, A.W.(2004).Capacitative calcium entry in guinea pig gallbladder smooth muscle in vitro.Life Sci.,74,1659-1669.
31. Rudorfer, M.V.,Potter, W.Z.(1999).Metabolism of tricyclic antidepressants.Cell. Mol. Neurobiol.,19,373-409.
32. Shideman, C.R.,Reinardy, J.L.,Thayer, S.A.(2009).gamma-Secretase activity modulates store-operated Ca2+ entry into rat sensory neurons.Neurosci. Lett.,451,124-128.
33. Song, Y.,Wilkins, P.,Hu, W.,Murthy, K.S.,Chen, J.,Lee, Z.,Oyesanya, R.,Wu, J.,Barbour, S.E.,Fang, X.(2007).Inhibition of calcium-independent phospholipase A2 suppresses proliferation and tumorigenicity of ovarian carcinoma cells.Biochem. J.,406,427-436.
34. Sudoh, Y.,Cahoon, E.E.,Gerner, P.,Wang, G.K.(2003).Tricyclic antidepressants as long-acting local anesthetics.Pain,103,49-55.
35. Suzuki, N.,Matsunaga, T.,Kanaho, Y.,Nozawa, Y.(1993).The mechanism of bradykinin-induced arachidonic acid release in osteoblast-like MC3T3-E1 cells phospholipase A2 activation by bradykinin and its regulation by protein kinase C and calcium.Nihon Seikeigeka Gakkai Zasshi,67,935-943.
36. Thastrup, O.,Cullen, P.J.,Drøbak, B.K.,Hanley, M.R.,Dawson, A.P.(1990).Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase.Proc. Natl. Acad. Sci. USA,87,2466-2470.
37. Thompson, A.K.,Mostafapour, S.P.,Denlinger, L.C.,Bleasdale, J.E.,Fisher, S.K.(1991).The aminosteroid U-73122 inhibits muscarinic receptor sequestration and phosphoinositide hydrolysis in SK-N-SH neuroblastoma cells. A role for Gp in receptor compartmentation.J. Biol. Chem.,266,23856-23862.
38. Tsien, R.Y.(1980).New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures.Biochemistry,19,2396-2404.
39. Van Esch, G.J.(1986).Toxicology of tert-butylhydroquinone (TBHQ).Food Chem. Toxicol.,24,1063-1065.
40. Wang, J.L.,Chou, C.T.,Liu, K.,Liang, W.Z.,Cheng, J.S.,Chang, H.T.,Chen, I.S.,Lu, T.,Kuo, C.C.,Yu, C.C.,Shieh, P.,Kuo, D.H.,Chen, F.A.,Jan, C.R.(2016).Ca2+ signaling and cell death induced by protriptyline in HepG2 human hepatoma cells.J. Biochem. Mol. Toxicol.,30,539-547.
41. Woodsome, T.P.,Eto, M.,Everett, A.,Brautigan, D.L.,Kitazawa, T.(2001).Expression of CPI-17 and myosin phosphatase correlates with Ca2+ sensitivity of protein kinase C-induced contraction in rabbit smooth muscle.J. Physiol.,535,553-564.
42. Woolf, A.D.,Erdman, A.R.,Nelson, L.S.,Caravati, E.M.,Cobaugh, D.J.,Booze, L.L.,Wax, P.M.,Manoguerra, A.S.,Scharman, E.J.,Olson, K.R.,Chyka, P.A.,Christianson, G.,Troutman, W.G.(2007).Tricyclic antidepressant poisoning: an evidencebased consensus guideline for out-of-hospital management.Clin. Toxicol.,45,203-233.
43. Wooltorton, J.R.,Mathie A.(1995).Potent block of potassium currents in rat isolated sympathetic neurones by the uncharged form of amitriptyline and related tricyclic compounds.Brit. J. Pharmacol.,116,2191-2200.
44. Zhang, Z.,Du, X.,Zhao, C.,Cao, B.,Zhao, Y.,Mao, X.(2013).The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma.Anticancer Drugs,24,792-798.