The Role of Uroguanylin in Regulation of Ion Transport in Salivary Glands

Overview

Journal Acta Stomatol Croat

Specialty Dentistry

Date 2023 Oct 9

PMID 37808412

Authors

Domagoj Jakovac

Martina Ratko

Iva Marolt Banek

Ivana Lapic

Aleksandra Dugandzic

Affiliations

Soon will be listed here.

Abstract

Objectives: Guanylin peptides are considered to be the only intrinsic regulators of salivary glands secretion. Therefore, the aim of this study was to determine the effects of systemic uroguanylin (UGN) of the salivary flow and ion composition. Besides, the objective was to investigate whether those effects include activation of guanylate cyclase C (GC-C).

Material And Methods: This study was conducted on 7 months old C57Bl6NCrl (wild type, WT) and GC-C knockout (KO) mice. Salivary flow rate and ion composition were determined after pilocarpine stimulation with UGN (30 µg/animal) or saline i.p. application. The expression of mRNA for AQPs, NHEs, NBCn1, Slc26a3/a6 and CFTR were determined by qPCR in submandibular salivary glands.

Results: When applied i.p., UGN decreased the pilocarpine stimulated saliva flow rate and increased the concentration of Na, H and Cl. In GC-C KO mice, UGN showed no effect on saliva flow rate, while the concentrations of Na, H and Cl are the same in GC-C KO littermates when compared to WT mice. UGN increased expression of Slc26a6 while in GC-C KO mice Slc26a6 had a higher expression when compared to WT mice, suggesting involvement of GC-C independent signalling pathway for UGN. The difference in Slc26a6 in GC-C KO mice is not unique for salivary glands because it was also found in duodenum and kidney cortex.

Conclusions: The effects of UGN via basolateral membrane of salivary glands cells have not been considered up to date. In our study, UGN, when applied i.p., decreased salivary flow rate, pH, and changed the composition of other ions. Therefore, plasma UGN, an hour after a meal, could have physiological and pathological importance (development of cavities, inflammations or demineralizations), and the inhibition of systemic UGN effects could be considered a new approach in treatment of those conditions.

References

Gautam D, Heard T, Cui Y, Miller G, Bloodworth L, Wess J . Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice. Mol Pharmacol. 2004; 66(2):260-7. DOI: 10.1124/mol.66.2.260. View

Lorenz J, Nieman M, Sabo J, Sanford L, Hawkins J, Elitsur N . Uroguanylin knockout mice have increased blood pressure and impaired natriuretic response to enteral NaCl load. J Clin Invest. 2003; 112(8):1244-54. PMC: 213491. DOI: 10.1172/JCI18743. View

Habek N, Ratko M, Dugandzic A . Uroguanylin increases Ca2+ concentration in astrocytes via guanylate cyclase C-independent signaling pathway. Croat Med J. 2021; 62(3):250-263. PMC: 8275953. View

Hamra F, Forte L, Eber S, Pidhorodeckyj N, Krause W, Freeman R . Uroguanylin: structure and activity of a second endogenous peptide that stimulates intestinal guanylate cyclase. Proc Natl Acad Sci U S A. 1993; 90(22):10464-8. PMC: 47797. DOI: 10.1073/pnas.90.22.10464. View

Krause W, Freeman R, Fort L . Autoradiographic demonstration of specific binding sites for E. coli enterotoxin in various epithelia of the North American opossum. Cell Tissue Res. 1990; 260(2):387-94. DOI: 10.1007/BF00318641. View

Sindic A, Velic A, Basoglu C, Hirsch J, Edemir B, Kuhn M . Uroguanylin and guanylin regulate transport of mouse cortical collecting duct independent of guanylate cyclase C. Kidney Int. 2005; 68(3):1008-17. DOI: 10.1111/j.1523-1755.2005.00518.x. View

Park S, Shcheynikov N, Hong J, Zheng C, Suh S, Kawaai K . Irbit mediates synergy between ca(2+) and cAMP signaling pathways during epithelial transport in mice. Gastroenterology. 2013; 145(1):232-241. PMC: 3696401. DOI: 10.1053/j.gastro.2013.03.047. View

Bianciotti L, Elverdin J, Vatta M, Colatrella C, Fernandez B . Atrial natriuretic factor enhances induced salivary secretion in the rat. Regul Pept. 1994; 49(3):195-202. DOI: 10.1016/0167-0115(94)90141-4. View

Kita T, Smith C, Fok K, Duffin K, MOORE W, Karabatsos P . Characterization of human uroguanylin: a member of the guanylin peptide family. Am J Physiol. 1994; 266(2 Pt 2):F342-8. DOI: 10.1152/ajprenal.1994.266.2.F342. View

10.

Schulz S, Chrisman T, Garbers D . Cloning and expression of guanylin. Its existence in various mammalian tissues. J Biol Chem. 1992; 267(23):16019-21. View

11.

Bianciotti L, Elverdin J, Vatta M, Fernandez B . Atrial natriuretic factor modifies the composition of induced-salivary secretion in the rat. Regul Pept. 1996; 65(2):139-43. DOI: 10.1016/0167-0115(96)00083-3. View

12.

THAYSEN J, THORN N, SCHWARTZ I . Excretion of sodium, potassium, chloride and carbon dioxide in human parotid saliva. Am J Physiol. 1954; 178(1):155-9. DOI: 10.1152/ajplegacy.1954.178.1.155. View

13.

Vaandrager A, Bot A, Ruth P, Pfeifer A, Hofmann F, de Jonge H . Differential role of cyclic GMP-dependent protein kinase II in ion transport in murine small intestine and colon. Gastroenterology. 1999; 118(1):108-14. DOI: 10.1016/s0016-5085(00)70419-7. View

14.

Fawcus K, Gorton V, Lucas M, McEwan G . Stimulation of three distinct guanylate cyclases induces mucosal surface alkalinisation in rat small intestine in vitro. Comp Biochem Physiol A Physiol. 1997; 118(2):291-5. DOI: 10.1016/s0300-9629(96)00307-6. View

15.

Carrithers S, Ott C, Hill M, Johnson B, Cai W, Chang J . Guanylin and uroguanylin induce natriuresis in mice lacking guanylyl cyclase-C receptor. Kidney Int. 2003; 65(1):40-53. DOI: 10.1111/j.1523-1755.2004.00375.x. View

16.

Kulaksiz H, Rehberg E, Stremmel W, Cetin Y . Guanylin and functional coupling proteins in the human salivary glands and gland tumors : expression, cellular localization, and target membrane domains. Am J Pathol. 2002; 161(2):655-64. PMC: 1850736. DOI: 10.1016/S0002-9440(10)64221-6. View

17.

Miyazato M, Nakazato M, Matsukura S, Kangawa K, Matsuo H . Uroguanylin gene expression in the alimentary tract and extra-gastrointestinal tissues. FEBS Lett. 1996; 398(2-3):170-4. DOI: 10.1016/s0014-5793(96)01235-5. View

18.

Jaleel M, London R, Eber S, Forte L, Visweswariah S . Expression of the receptor guanylyl cyclase C and its ligands in reproductive tissues of the rat: a potential role for a novel signaling pathway in the epididymis. Biol Reprod. 2002; 67(6):1975-80. DOI: 10.1095/biolreprod.102.006445. View

19.

Su S, Rugis J, Wahl A, Doak S, Li Y, Suresh V . A Mathematical Model of Salivary Gland Duct Cells. Bull Math Biol. 2022; 84(8):84. PMC: 9262821. DOI: 10.1007/s11538-022-01041-3. View

20.

Ganguly U, Chaudhury A, Basu A, Sen P . STa-induced translocation of protein kinase C from cytosol to membrane in rat enterocytes. FEMS Microbiol Lett. 2001; 204(1):65-9. DOI: 10.1111/j.1574-6968.2001.tb10864.x. View