Top

Published in:

01-04-2004 | Original Article

Ontogeny of guanylin-immunoreactive cells in rat salivary glands

Authors: R. Vaccaro, Y. Cetin, T. G. Renda

Published in: Brain Structure and Function | Issue 1/2004

Abstract

Guanylin-like peptides regulate electrolyte/water transport through the epithelia. Moreover, these peptides possess antiproliferative activity and regulate the turnover of epithelial cells. In an earlier study we localized guanylin immunoreactivity in secretory ducts of adult rodent salivary glands. In this study we investigated the appearance and distribution pattern of this peptide during the development of rat salivary glands. Guanylin immunoreactivity appeared at the beginning of cell differentiation from solid bud, on embryonic day 17 in the submandibular and sublingual glands and after day 18 in the parotid gland. Guanylin immunoreactivity appeared first in ductal and acinar anlage: its cell distribution pattern and fate differed in these two compartments. In the duct cells guanylin immunoreactivity spread after the duct system developed, whereas in acinar cells it disappeared after cell differentiation. The guanylin immunoreactivity we detected in adult salivary duct cells accords with guanylin’s role in regulating electrolyte and water transport through the various epithelia. It does so by activating guanylate cyclase-C receptor, increasing intracellular cGMP concentration, and phosphorylating the cystic fibrosis transmembrane conductance regulator (CFTR) protein by the cGMP-dependent protein kinase II. This signaling cascade couples to the ductal electrolyte/water secretion and modulates finally the electrolyte composition of the saliva. On the other hand, CFTR is also involved in mechanisms of cell growth, by regulating apoptosis, and promoting cell differentiation. The early diffuse guanylin immunoreactivity we observed in ducts and acinar anlage, before the secretory set is operative, suggests guanylin has a role in cell differentiation.

Alvares EP, Sesso A (1975) Cell proliferation, differentiation and transformation in the rat submandibular gland during early postnatal growth. A quantitative and morphological study. Arch Histol Jap 38:177–208PubMed

Barriere H, Poujeol C, Tauc M, Blasi JM, Counillon L, Poujeol P (2001) CFTR modulates programmed cell death by decreasing intracellular pH in Chinese hamster lung fibroblasts. Am J Physiol Cell Physiol 281:C810–C824PubMed

Beltowski J (2001) Guanylin and related peptides. J Physiol Pharmacol 52:351–375PubMed

Bottaro B, Cutler LS (1984) An electrophysiological study of the postnatal development of the autonomic innervation of the rat submandibular salivary gland. Archs Oral Biol 29:237–242

Carrithers SL, Parkinson SJ, Goldstein S, Park P, Robertson DC, Waldman SA (1994) Escherichia coli Heat-Stable toxin receptors in human colonic tumors. Gastroenterology 107:1653–1661PubMed

Carrithers SL, Barber MT, Biswas S, Parkinson SJ, Park PK, Goldstein SD, Waldman SA (1996A) Guanylil cyclase C is a selective marker for metastatic colorectal tumors in human extraintestinal tissues. Proc Natl Acad Sci USA 93:14827–14832CrossRefPubMed

Carrithers SL, Parkinson SJ, Goldstein S, Park P, Urbanski RW, Waldman SA (1996B) Escherichia coli Heat-Stable toxin receptors a novel marker for colorectal tumors. Dis Colon Rectum 39:171–181PubMed

Cetin Y, Kuhn M, Kulaksiz H, Aderman K, Bargsten G, Grube D, Forssmann WG (1994) Enterochromaffin cells in the digestive system: cellular source of guanylin, a guanylate cyclase-activating peptide. Proc Natl Acad Sci USA 91:2935–2939PubMed

Cetin Y, Kulaksiz H, Redecker P, Bargsten G, Adermann K, Grube D, Forssmann WG (1995) Bronchiolar nonciliated secretory (Clara) cells: source of guanylin in the mammalian lung. Proc Natl Acad Sci USA 92:5925–5929PubMed

Chang WWL (1974) Cell population changes during acinus formation in the postnatal rat submandibular gland. Anat Rec 178:187–201PubMed

Cohen MB, Moyer MS, Luttrell M, Giannella RA (1986) The immature rat small intestine exhibits an increased sensitivity and response to Escherichia coli heat-stable enterotoxin. Pediatr Res 20:555–560PubMed

Cohen MB, Guarino A, Shukla R, Giannella RA (1988) Age-related differences in receptors for Escherichia coli heat-stable enterotoxin in the small and large intestine of children. Gastroenterology 94:367–373PubMed

Cohen MB, Witte DP, Hawkins JA, Currie MG (1995) Immunohistochemical localization of guanylin in the rat small intestine and colon. Biochem biophys res commun 209:803–808CrossRefPubMed

Cohen MB, Hawkins JA, Witte DP (1998) Guanylin mRNA expression in human intestine and colorectal adenocarcinoma. Lab Invest 78:101–108PubMed

Cutler LS (1980) The development and independent relationships between morphogenesis in developing salivary gland secretory cells. Anat Rec 196:341–347PubMed

Cutler LS, Chaudhry AP (1974) Cytodifferentiation of the acinar cells of the rat submandibular gland. Dev Biol 41:31–41PubMed

Cutler LS, Chaudhry AP (1975) Cytodifferentiation of striated duct cells and secretory cells in the convoluted granular tubules of the rat submandibular gland. Am J Anat 143:201–218PubMed

Date Y, Nakazato M, Yamaguchi H, Miyazato M, Matsukura S (1996) Tissue distribution and plasma concentration of human guanylin. Intern Med 35:171–175PubMed

D’Este L, Kulaksiz H, Rausch U, Vaccaro R, Wenger T, Tokunaga Y, Renda TG, Cetin Y (2000) Expression of guanylin in “pars tuberalis-specific cells” and gonadotrophs of rat adenohypophysis. Proc Natl Acad Sci USA 97:1131–1136CrossRefPubMed

Gali H, Sieckman GL, Hoffman TJ, Kiefer GE, Chin DT, Forte LR, Volkert WA (2001A) Synthesis and in vitro evaluation of an 111In-labeled ST-peptide enterotoxin (ST) analogue for specific targeting of guanylin receptors on human colonic cancers. Anticancer Res 21:2785–2792PubMed

Gali H, Sieckman GL, Hoffman TJ, Owen NK, Chin DT, Forte LR, Volkert WA (2001B) In vivo evaluation of an 111In-labeled ST-peptide analog for specific-targeting of human colon cancers. Nucl Med Biol 28:903–909CrossRefPubMed

Garrett JR, Thulin A (1975) Changes in parotid acinar cells accompanying salivary secretion in rats on sympathetic or parasympathetic nerve stimulation. Cell Tiss Res 159:179–193

Gresik EW (1980) Postnatal developmental changes in submandibular glands of rats and mice. J Histochem Cytochem 28:860–870PubMed

Gresik EW (1994) The granular convoluted tubule (GCT) cells of rodent submandibular glands. Microsc Res Tech 27:1–24PubMed

Guarino A, Cohen MB, Giannella RA (1987) Small and large intestinal guanylate cyclase activity in children: effect of age and stimulation by Escherichia coli heat-stable enterotoxin. Pediatr Res 21:551–555PubMed

Hayashi H, Ozono S, Watanabe K, Nagatsu I, Onozuka M (2000). Morphological aspects of the postnatal development of submandibular glands in male rats: involvement of apoptosis. J Histochem Cytochem 48:695–698PubMed

Ieda H, Naruse S, Furuya S, Ozaki T, Ando E, Nokihara K, Hori S, Kitagawa M, Hayakawa T (1998) Coexistence of proguanylin (1–15) and somatostatin in the gastrointestinal tract. J Gastroenterol Hepatol 13:1225–1233CrossRefPubMed

Izutsu KT, Cantino ME, Johnson DE (1994) A review of electron probe X-ray microanalysis studies of salivary gland cells. Microsc Res Tech 27:71–79PubMed

Jacoby F, Leeson CR (1959) The post-natal development of the rat submaxillary gland. J Anat 93:201–216PubMed

Klein RM (1982). Acinar cell proliferation in the parotid and submandibular salivary glands of neonatal rat. Cell Tissue Kinet 15:187–195PubMed

Kulaksiz H, Schmid A, Hönscheid M, Eissele R, Klempnauer J, Cetin Y (2001A) Guanylin in the human pancreas: a novel luminocrine regulatory pathway of electrolyte secretion via cGMP and CFTR in the ductal system. Histochem Cell Biol 115:131–145CrossRefPubMed

Kulaksiz H, Rausch U, Vaccaro R, Renda TG, Cetin Y (2001B) Guanylin and uroguanylin in the parotid and submandibular glands: potential intrinsic regulators of electrolyte secretion in salivary glands. Histochem Cell Biol 115:527–533PubMed

Kulaksiz H, Rehberg E, Stremmel W, Cetin Y (2002) Guanylin and functional coupling proteins in the human salivary glands and gland tumors: expression, cellular localization, and target membrane domains. Am J Pathol 161:655–664PubMed

Lawson KA (1970) Morphogenesis and functional differentiation of the rat parotid gland in vivo and in vitro. J Embryol Exp Morph 24:411–424PubMed

Li CY, Ziesmer SC, Lazcano-Villareal O (1987) Use of azide and hydrogen peroxide as an inhibitor for endogenous peroxidase in the immunoperoxidase method. J Histochem Cytochem 35:1547–1460

Li Z, Taylor-Blake B, Light A, Goy MF (1995) Guanylin, an endogenous ligand for C-type guanylate cyclase, is produced by goblet cells in the rat intestine. Gastroenterology 109:1863–1875PubMed

Martinez JR, Camden J (1989) Ca²⁺ mobilization and Cl efflux in submandibular salivary cells of adult and newborn rats. Arch Oral Biol 34:147–152PubMed

Mori M, Yamada K, Ohomura H, Wataru K, Takai Y, Ilg E, Schäfer BW, Heizmann CW (1998) Immunohistochemical localization of S100A1 and S100A6 in postnatally developing salivary glands of the rats. Histochem Cell Biol 110:579–587CrossRefPubMed

Mork A-C, Zhang A, Martinez R, Roomans GM (1996) Chloride secretion in the submandibular gland of adult and early postnatal rats studied by X-ray microanalysis. Histochem Cell Biol 105:297–303PubMed

Pinkstaff CA (1980) The cytology of salivary glands. Int Rev Cytol 63:141-261

Pitari GM, Guglielmo MD, Park J, Schulz S, Waldman SA (2001) Guanylyl cyclase C agonists regulate progression through the cell cycle of human colon carcinoma. Proc Natl Acad Sci USA 98:7846–7851CrossRefPubMed

Redman RS (1995) Proliferative activity by cell type in the developing rat parotid gland. Anat Rec 241:529–540PubMed

Redman RS, Ball WD (1978) Cytodifferentiation of secretory cells in the sublingual gland of the prenatal rat: a histological, histochemical and ultrastructural study. Am J Anat 153:367–390PubMed

Reinecke M, David I, Loffing-Cueni D, Ablinger P, Cetin Y, Kuhn M, Forssmann WG (1996) Localization, expression, and characterization of guanylin in the rat adrenal medulla. Histochem Cell Biol 106:367–374CrossRefPubMed

Shailubhai K (2002) Therapeutic applications of guanylate cyclase-C receptor agonists. Curr Opin Drug Discov Devel 5:261–268PubMed

Shailubhai K, Yu HH, Karunanandaa K, Wang JY, Eber SL, Wang Y, Joo NS, Kim HD, Miedema BW, Abbas SZ, Boddupalli SS, Currie MG, Forte LR (2000) Uroguanylin treatment suppresses polyp formation in the Apc(Min/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP. Cancer Res 60:5151–5157PubMed

Sivakumar S, Mirels L, Miranda AJ, Hand AR (1998) Secretory protein expression patterns during rat parotid gland development. Anat Rec 252:485–497CrossRefPubMed

Srinivasan R, Chang WWL (1975) The development of the granular convoluted duct in the rat submandibular gland. Anat Rec 182:29–40PubMed

Steinbrecher KA, Tuohy TMF, Heppner Goss K, Scott MC, Witte D, Groden J, Cohen MB (2000) Expression of guanylin is downregulated in mouse and human intestinal adenomas. Biochem Biophys Res Commun 273:225–230CrossRefPubMed

Yamashina S, Mizuhira V (1976) Postnatal development of acinar cells in rat submandibular as revealed by electron microscopic staining for carbohydrate. Am J Anat 146:211–235PubMed

Title: Ontogeny of guanylin-immunoreactive cells in rat salivary glands
Authors: R. Vaccaro
Y. Cetin
T. G. Renda
Publication date: 01-04-2004
Publisher: Springer-Verlag
Published in: Brain Structure and Function / Issue 1/2004
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-003-0375-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Ontogeny of guanylin-immunoreactive cells in rat salivary glands

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2004

Ultrastructural localization of gastrin-releasing peptide (GRP) in the uterine gland of cow

Glutamic acid decarboxylase immunoreactive large neuron types in the granular layer of the human cerebellar cortex

Palatal shelf movement during palatogenesis: a fate map of the fetal mouse palate cultured in vitro

Acknowledgement to reviewers 2003

Decamethonium bromide-mediated inhibition of embryonic muscle development

Embryonic development of the ganglion plexuses and the concentric layer structure of human gut: a topographical study