INFLUENCE OF CANNABINOID RECEPTOR GPR55 UPON SALIVATION OF RAT SUBMANDIBULAR SALIVARY GLAND

S. Y. Korchynska, R. E. Makarovska, N. V. Fedirko


DOI: http://dx.doi.org/10.30970/sbi.0703.314

Abstract


This paper is devoted to elucidation of functionally active cannabinoid receptor GPR55 in submandibular salivary gland cells of rats by introducing a specific agonist lysophosphatidylinositol. We studied the effect of GPR55 activation on the following parameters of basal salivation in vivo: rate of salivation of protein concentration and electrolytes. It was shown that in vivo activation of cannabinoid receptor GPR55 in the acinar cells of submandibular salivary gland by lysophosphatidylinositol caused a dose-dependent reduction in basal flow of saliva. We also elucidated that activation of the cannabinoid receptor GPR55 induced an increase of concentration of total protein in saliva secreted in vivo. That indicate that the activation of cannabinoid receptor GPR55 leads to an enhancement of exocytosis of secretory vesicles in acinar cells. We showed that under conditions of activation of cannabinoid receptor GPR55, changes also occured in concentration of electrolytes in basal saliva such as: reduction in concentration of calcium (Ca2+), inorganic phosphorus (Pi), and increasing concentration of potassium (K+). Based on these findings, we suggest that activation of cannabinoid receptor GPR55 leads to modulation of intracellular signaling mechanisms involved in the secretion of water and electrolytes in acinar cells of rat submandibular salivary gland.


Keywords


submandibular salivary gland, cannabinoid receptor GPR55, lysophosphatidylinositol, basal salivation

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. Abood M.E., Sorensen R.G., Nephi S. Endocannabinoids: Actions at Non-CB1/CB2 Cannabinoid Receptors. ISBN, 2013; 978: 4614-4669.

5. Barnett R.N., Skodon S.B., Goldberg M.H. Performance of "kits" used for clinical chemical analysis of calcium in serum. Am. J. Clin. Pathol,1973; 59: 836-845.
https://doi.org/10.1093/ajcp/59.6.836
PMid:4709082

6. Bondarenko A., Waldeck-Weiermair M., Graier W.F. GPR55-dependent and -independent ion signaling in response to lysophosphatidylinositol in endothelial cells. British Journ. of Pharmacology, 2010; 161: 308-320.
https://doi.org/10.1111/j.1476-5381.2010.00744.x
PMid:20735417 PMCid:PMC2931756

7. Duncan M., Mouihate A., Mackie K. Cannabinoid CB2 receptors in the enteric nervous system modulate gastrointestinal contractility in lipopolysaccharide-treated rats. Am. J. Physiol. Gastrointest. Liver Physiol, 2008; 295: G78-G87.
https://doi.org/10.1152/ajpgi.90285.2008
PMid:18483180 PMCid:PMC2494728

8. Freund T.F., Katona I., Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol. Rev, 2003; 83: 1017-1066.
https://doi.org/10.1152/physrev.00004.2003
PMid:12843414

9. Henry R. J. Clinical Chemistry - Principles and Techniques. Harper and Row, New York, 1974; 664-666.

10. Henstridge C. M., Balenga A. B., Ford L. A. The GPR55 ligand L-α-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation. The FASEB Journ, 2009; 23: 183-193.
https://doi.org/10.1096/fj.08-108670
PMid:18757503

11. Hiley C.R., Kaup S.S. GPR55 and the vascular receptors for cannabinoids. British Journ. of Pharmacology, 2007; 152: 559-561.
https://doi.org/10.1038/sj.bjp.0707421
PMid:17704825 PMCid:PMC2190021

12. Hillmann J.J. Biochemical and Clinical Actions. Clin.Chem. and Clin. Biochem, 1967; 5: 93-95.

13. Kano M., Ohno-Shosaku T., Hashimotodani Y. Endocannabinoid-mediated control of synaptic transmission. Physiol. Rev, 2009; 89: 309-380.
https://doi.org/10.1152/physrev.00019.2008
PMid:19126760

14. Kikuchi A., Ohashi K., Sugie Y. Pharmacological evaluation of a novel cannabinoid 2 (CB2) ligand, PF-03550096, in vitro and in vivo by using a rat model of visceral hypersensitivity. J. Pharmacol. Sci, 2008; 106: 219-224.
https://doi.org/10.1254/jphs.FP0071599
PMid:18270474

15. Kopach O., Vats J., Netsyk O. Cannabinoid receptors in submandibular acinar cells: functional coupling between saliva fluid and electrolytes secretion and Ca2+ signalling. J. Cell Sci, 2012; 125(Pt 8): 1884-95
https://doi.org/10.1242/jcs.088930
PMid:22366450

16. Lauckner J.E., Jensen J.B., Chen Huei-Ying. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. PNAS, 2008; 105(7): 2699-2704.
https://doi.org/10.1073/pnas.0711278105
PMid:18263732 PMCid:PMC2268199

17. Lowry O.H., Rosebrough N.J., Farr L.A. Protein measurement with the folin phenol reagent. J. Biol. Chem, 1951; 193: 265-275.

18. 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

19. Matsuda L.A. Molecular aspects of cannabinoid receptors. Crit. Rev. Neurobiol, 1997; 11: 143-166.
https://doi.org/10.1615/CritRevNeurobiol.v11.i2-3.30
PMid:9209828

20. Matsuda L A., Lolait S.J., Brownstein M.J. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 1990; 346: 561-564.
https://doi.org/10.1038/346561a0
PMid:2165569

21. 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

22. Pertwee R.G. GPR55: a new member of the cannabinoid receptor clan? Br. J. Pharmacol, 2007; 152(7): 984-986.
https://doi.org/10.1038/sj.bjp.0707464
PMid:17876300 PMCid:PMC2095104

23. Pertwee R.G. Cannabinoids and the gastrointestinal tract. Gut, 2001; 48: 859-867.
https://doi.org/10.1136/gut.48.6.859
PMid:11358910 PMCid:PMC1728337

24. 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

25. Sanger G.J. Endocannabinoids and the gastrointestinal tract: what are the key questions? Br. J. Pharmacol, 2007; 152: 663-670.
https://doi.org/10.1038/sj.bjp.0707422
PMid:17767170 PMCid:PMC2190011

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

27. Wright K.L., Duncan M., Sharkey K.A. Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation. Br. J. Pharmacol, 2008; 153: 263-270.
https://doi.org/10.1038/sj.bjp.0707486
PMid:17906675 PMCid:PMC2219529


Refbacks

  • There are currently no refbacks.


Copyright (c) 2013 Studia biologica

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.