CB1 AND CB2 CANNABINOIDS RECEPTORS REGULATE BASAL SALIVATION AND PROTEIN-ELECTROLYTE SALIVA CONTENT VIA MODULATION OF АТPase SYSTEMS FUNCTIONING IN THE ACINAR CELLS FROM SUBMANDIBULAR SALIVARY GLAND

O. Netsyk, O. Kopach, N. Fedirko


DOI: http://dx.doi.org/10.30970/sbi.0402.099

Abstract


We showed that activation in vivo of СВ1 та СВ2 cannabinoids receptors (СBRs) of submandibular salivary gland with selective agonist WIN 55212-2 caused suppression of basal salivation and alteration of saliva content. Similar type of changes were observed after single administration of endocannabinoid and in the conditions of prolonged agonist use. Maximal suppression we observed at 10 min after single application of WIN 55212-2 (~ 45%) and ~ 60% – in the conditions of prolonged administration of an agonist. Prolonged treatmnent with WIN 55212-2 leads to acidification of secreted saliva (рН ~ 9.0-8.8), increase in saliva Ca2+ and protein concentration as well as α-amylase activity. Any significant changes of K+, Na+, P2+ concentrations in saliva were observed upon activation of СBRs. We also showed that decrease of basal salivation is accompanied by inhibition of Na+/K+-АТP-ase and endoplasmic reticulum Са2+-АТP-ase but increased activity of plasma membrane Са2+-АТP-ase. Therefore upon activation of СBRs: і) c-АМP-mediated signaling system that contribute to the protein secretion increases activity; іі) transcellular H2O transport that contribute to the fluid secretion is reduced forming the base of inbition of basal salivation; ііі) electrolyte saliva content remains unaltered that can be attributed to the unaltered functioning of the ductal cells unlike acinar cells. Concluding, we suggest that observed changes of saliva рН and activity of АТP-ase systems in acinar cells contribute to the СBRs-mediated inhibition of basal salivation provided by submandibular salivary gland.


Keywords


cannabinoid receptors, WIN 55212-2, submandibular salivary gland, salivation, ATP-ase activity

References


1. Копач О., Федірко Н. Кальцій-залежні зміни функціонування ацинарних клітин слинних залоз у разі дії агоністів холінергічної природи. Вісник Львів. ун-ту. Сер. біол, 2004; 37: 205-212.

2. Нецик О., Гричан Н., Копач О., Федірко Н. Роль канабіноїдних рецепторів у регуляції слиновиділення підщелепною слинною залозою щурів. Вісник Львів. ун-ту. Сер. біол, 2009; 50: 131-143.

3. Нецик О., Федірко Н. Ендоканабіноїди регулюють процеси слиновиділення через модуляцію процесів кальцієвої сигналізації. Вісник Львів. ун-ту. Сер. біол, 2010; 52: 152-162.

4. Agarwal R.P., Henkin R.I. Metal binding characteristics of human salivary and porcine pancreatic amylase. J. Biol. Chem, 1987; 262: 2568- 2575.

5. Ambudkar I.S. Regulation of calcium in salivary gland secretion. Crit. Rev. Oral. Biol. Med, 2000; 11(1): 4-25.
https://doi.org/10.1177/10454411000110010301

6. Ashby M.C., Tepikin A.V. Polarized calcium and calmodulin signaling in secretory epithelia. Physiol. Rev, 2002; 82: 701-734.
https://doi.org/10.1152/physrev.00006.2002
PMid:12087133

7. Belan P., Gardner J., Gerasimenko O. et al. Isoproterenol evokes extracellular Ca2+ spikes due to secretory events in salivary gland cells. J. Biol. Chem, 1998; 273: 4106-4111.
https://doi.org/10.1074/jbc.273.7.4106

8. Bloom A.S., Haavik C.O., Strehlow D. Effects of D9-tetrahydrocannabinol on ATPases in mouse brain subcellular fractions. Life Sci,1978; 23:1399-404.
https://doi.org/10.1016/0024-3205(78)90400-9

9. Brown E.M., MacLeod R.J. Extracellular calcium sensing and extracellular calcium signaling. Physiol. Rev, 2001; 81: 239-297.
https://doi.org/10.1152/physrev.2001.81.1.239
PMid:11152759

10. Bruce J.I., Yang X., Ferguson C.J. et al. Molecular and functional identification of a Ca2+ (polyvalent cation)-sensing receptor in rat pancreas. J. Biol. Chem, 1999; 274: 20561-20568.
https://doi.org/10.1074/jbc.274.29.20561
PMid:10400686

11. Burnstein L.S., Boskey A.L., Tannenbaum P.J et al. The crystal chemistry of submandibular and parotid salivary gland stones. J. Oral. Pathol, 1979; 8: 284-291.
https://doi.org/10.1111/j.1600-0714.1979.tb01830.x

12. Busch L., Sterin-Borda L., Borda E. Expression and biological effects of CB1 cannabinoid receptor in rat parotid gland. Biochemical Pharmacology, 2004; 68: 1767-1774.
https://doi.org/10.1016/j.bcp.2004.06.029
PMid:15450942

13. Caroppo R., Gerbino A., Debellis Le t al. Asymmetrical, agonist-induced fluctuations in local extracellular [Ca2+] in intact polarized epithelia. EMBO J, 2001; 20: 6316-6326.
https://doi.org/10.1093/emboj/20.22.6316
PMid:11707403 PMCid:PMC125728

14. Catalan M.A., Nakamoto T., Melvin J.E. The salivary gland fluid secretion mechanism. The Journal of Medical Investigation, 2009; 56: 192-196.
https://doi.org/10.2152/jmi.56.192
PMid:20224180

15. Cook D.I., Van Lennep E.W., Roberts M.L., Young J.A. Secretion by the major salivary glands. Physiology of the Gastrointestinal Tract. Ed. LR Johnson, New York: Raven Press, 1994. 1061-17 p.

16. Darling M.R. Cannabis abuse and oral health care: review and suggestions for management. SADJ, 2003; 58(5): 189-90.

17. Fedirko N., Klevets M., Vats Ju. Isolated acini as an object for the investigation of the Ca2+-transporting system of the secretory cell membranes. Neurophysiology, 2000; 32 (3): 183-184.
https://doi.org/10.1007/BF02506541

18. Fedirko N.V., Kruglikov I.A., Kopach O.V. et al. Changes in functioning of rat submandibular salivary gland under streptozotocin-induced diabetes are associated with alterations of Ca2+ signaling and Ca2+ transporting pumps. BBA, 2006; 1762: 294-303.
https://doi.org/10.1016/j.bbadis.2005.12.002
PMid:16443349

19. Fernandez-Solari J., Prestifilippo J.P., Vissio P. et al. Anandamide injected into the lateral ventricle of the brain inhibits submandibular salivary secretion by attenuating parasympathetic neurotransmission. Braz. J. Med. Biol. Res, 2009; 42(6): 537-544.
https://doi.org/10.1590/S0100-879X2009000600010
PMid:19448903

20. Gleeson D., Hood K.A., Murphy G.M., Dowling R.H. Calcium and carbonate ion concentrations in gallbladder and hepatic bile. Gastroenterology, 1992; 102: 1707-1716.
https://doi.org/10.1016/0016-5085(92)91734-L

21. Howlett A.C., Barth F., Bonner T.I. et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol. Rev, 2002; 54(2): 161-202.
https://doi.org/10.1124/pr.54.2.161
PMid:12037135

22. Kim M.H., Sekijima J., Lee S.P. Primary intrahepatic stones. Am. J. Gastroenterol, 1995; 90: 540-548.

23. Laurent B., Roy P.E., Gailis L. Inhibition by D 1-tetrahydrocannabinol of a Na+-K+ transport ATPase from rat ileum. Preliminary report. Can. J. Physiol. Pharmacol, 1974; 52: 1110-1113.
https://doi.org/10.1139/y74-145
PMid:4281343

24. Lee M.G., Xu X., Zeng W. et al. Polarized expression of Ca2+ pumps in pancreatic and salivary gland cells. Role in initiation and propagation of [Ca2+]i waves. J. Biol. Chem, 1997; 272: 15771-15776.
https://doi.org/10.1074/jbc.272.25.15771
PMid:9188473

25. Marteau C., Gerolami A. Influence of hypercalcemia on ionized calcium concentration in pancreatic juice of the dog. J. Lab. Clin. Med, 1994; 123: 565-573.

26. Massa F., Storr M., Lutz B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J. Mol. Med, 2005; 83: 944-954.
https://doi.org/10.1007/s00109-005-0698-5
PMid:16133420

27. Matsuo S., Lagerlof F. Relationship between total and ionized calcium concentrations in human whole saliva and dental plaque fluid. Arch. Oral. Biol, 1991; 36: 525-527.
https://doi.org/10.1016/0003-9969(91)90146-L

28. McConnel W.R., Borzelleca J.F. A study of the mechanism of transport of delta9-tetrahydrocannabinol in the rat submaxillary gland in vitro. Arch. Int. Pharmacodyn. Ther, 1978; 235(2): 180-186.

29. Melvin J.E., Yule D., Shuttleworth T., Begenisich T. Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Annu. Rev. Physiol, 2005; 67: 445-469.
https://doi.org/10.1146/annurev.physiol.67.041703.084745
PMid:15709965

30. Moore E.W., Verine H.J. Pancreatic calcification and stone formation: a thermodynamic model of calcium in pancreatic juice. Am. J. Physiol. Gastrointest. Liver. Physiol, 1987; 252: G707-G718.
https://doi.org/10.1152/ajpgi.1987.252.5.G707
PMid:3107402

31. Pertwee R.G. The central neuropharmacology of cannabinoids. Pharmacol. Ther, 1988; 36: 189-261.
https://doi.org/10.1016/0163-7258(88)90106-4

32. Petersen O.H., Petersen C.C.H., Kasai H. Calcium and hormone action. Ann. Rev. Physiol, 1994; 56: 297-319.
https://doi.org/10.1146/annurev.ph.56.030194.001501
PMid:8010742

33. Prestifilippo J.P., Fernandez-Solari J., de la Cal, Iribarne M. et al. Inhibition of salivary secretion by activation of cannabinoid receptor. Exp Biol Med., 2006; 231: 1421-1429.
https://doi.org/10.1177/153537020623100816
PMid:16946411

34. Rinderknecht H. Pancreatic secretory enzymes. In: The Pancreas: Biology, Pathobiology and Disease. Ed. by Go VLW, Dimagno EP, Gardner JD, Lebenthal E. Reber H.A. and Scheele G.A. New York: Raven, 1993. 219 p.

35. Schramm W., Smith R.H., Craig P.A., Kidwell D.A. Drugs of abuse in saliva: a review. J. Anal. Toxicol, 1992; 16(1): 1-9.
https://doi.org/10.1093/jat/16.1.1
PMid:1640691

36. Shennan D.B., Peaker M. Transport of milk constituents by the mammary gland. Physiol. Rev., 2000; 80: 925-951.
https://doi.org/10.1152/physrev.2000.80.3.925
PMid:10893427

37. Sky-Peck H.H., Thuvasethakul P. Human pancreatic alpha-amylase. II. Effects of pH, substrate and ions on the activity of the enzyme. Ann. Clin. Lab. Sci, 1977; 7: 310-317.

38. Teufel H., Stock P., Rohrmoser H., Forell M.M. Calcium secretion in the isolated perfused canine pancreas. Res Exp Med., 1979; 176: 51-68.
https://doi.org/10.1007/BF01852111
PMid:523795

39. The endocannabinoid system. Handbook. ECSN, 2009. 96 p.
http://www.endocannabinoid.net/ECSHandbook

40. Turner R.J. Mehanisms of fluid secretion by salivary glands. Ann. NY Acad. Sci, 1993; 694: 24-35.
https://doi.org/10.1111/j.1749-6632.1993.tb18339.x
PMid:8215060

41. Verstraete A.G. Oral fluid testing for driving under the influence of drugs: history, recent progress and remaining challenges. Forensic Sci. Int, 2005; 150(2-3): 143-150.
https://doi.org/10.1016/j.forsciint.2004.11.023
PMid:15944054

42. Watson E.L., Jacobson K.L., Singh J.C. et al. The type 8 adenylyl cyclase is critical for Ca2+ stimulation of cAMP accumulation in mouse parotid acini. J. Biol. Chem, 2000; 275: 14691-91469.
https://doi.org/10.1074/jbc.275.19.14691
PMid:10799557


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