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

Domagoj Jakovac; Martina Ratko; Iva Marolt Banek; Ivana Lapić; Aleksandra Dugandžić

doi:10.15644/asc57/3/8

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

Acta Stomatol Croat. 2023 Sep;57(3):273-283. doi: 10.15644/asc57/3/8.

Authors

Domagoj Jakovac¹, Martina Ratko², Iva Marolt Banek¹, Ivana Lapić³, Aleksandra Dugandžić^{2

4}

Affiliations

¹ Department of Physiology, School of Dental Medicine, University of Zagreb, Croatia.
² Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Croatia.
³ Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia.
⁴ Department of Physiology, School of Medicine, University of Zagreb, Croatia.

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.

Keywords: Enterotoxin Receptors; GC-C Independent Signaling Pathway; MeSH Terms: Submandibular Gland; Pilocarpine; Saliva Flow Rate; Salivation; Stimulated Saliva Production; pH; qPCR.

University of Zagreb School of Dental Medicine.