Abstract
Ghrelin, a peptide hormone from the stomach, has been recently discovered to reduce sodium excretion from the kidney. Although the effects on the kidney suggest actions in the distal nephron, the sites of expression of ghrelin receptors have not been localised. In the present work we have used a mouse that expresses green fluorescent protein under the control of the ghrelin receptor promoter to locate sites of receptor expression in the kidney. Receptor expression was confined to the straight parts of the distal tubules and the thin limbs of the loops of Henle. No expression was detected in other structures, including the glomeruli, proximal tubules and collecting ducts. Ghrelin receptors were not found in extra-renal or intra-renal arteries, despite observations that ghrelin is a vasodilator. The distribution revealed by in situ hybridisation histochemistry was the same as that revealed by the reporter. In conclusion, ghrelin receptors have a restricted distribution in the kidney. The location in the straight parts of the distal tubules accords with observations that ghrelin promotes sodium retention.
References
Andrews ZB (2011) The extra-hypothalamic actions of ghrelin on neuronal function. Trends Neurosci 34:31–40
Ferens DM, Yin L, Bron R, Hunne B, Ohashi-Doi K, Sanger GJ, Witherington J, Shimizu Y, Furness JB (2010) Functional and in situ hybridisation evidence that preganglionic sympathetic vasoconstrictor neurons express ghrelin receptors. Neuroscience 166:671–679
Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S (1993) Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature 361:549–552
Hosoda H, Kojima M, Kangawa K (2006) Biological, physiological, and pharmacological aspects of ghrelin. J Pharmacol Sci 100:398–410
Howard AD, Feighner SD, Cully DF, Al E (1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273:974–977
Kemp BA, Howell NL, Gray JT, Keller SR, Nass RM, Padia SH (2011) Intrarenal ghrelin infusion stimulates distal nephron-dependent sodium reabsorption in normal rats. Hypertension 57:633–639
Kleinz MJ, Maguire JJ, Skepper JN, Davenport AP (2006) Functional and immunocytochemical evidence for a role of ghrelin and des-octanoyl ghrelin in the regulation of vascular tone in man. Cardiovasc Res 69:227–235
Kojima M, Kangawa K (2005) Ghrelin: structure and function. Physiol Rev 85:495–522
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660
Lambert E, Lambert G, Ika-Sari C, Dawood T, Lee K, Chopra R, Straznicky N, Eikelis N, Drew S, Tilbrook A, Dixon J, Esler M, Schlaich MP (2011) Ghrelin modulates sympathetic nervous system activity and stress response in lean and overweight men. Hypertension 57:1–8
Leite-Moreira AF, Soares J-B (2007) Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov Today 12:276–288
Matsumura K, Tsuchihashi T, Fujii K, Abe I, Iida M (2002) Central ghrelin modulates sympathetic activity in conscious rabbits. Hypertension 40:694–699
Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K (2001) Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol 280:R1483–R1487
Nielsen S, DiGiovanni SR, Christensen EI, Knepper MA, Harris HW (1993) Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci USA 90:11663–11667
Papotti M, Ghè C, Cassoni P, Catapano F, Deghenghi R, Ghigo E, Muccioli G (2000) Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab 85:3803–3807
Rossier BC (1997) Cum Grano Salis: The epithelial sodium channel and the control of blood pressure. J Am Soc Nephrol 8:980–992
Shinde UA, Desai KM, Yu C, Gopalakrishnan V (2005) Nitric oxide synthase inhibition exaggerates the hypotensive response to ghrelin: role of calcium-activated potassium channels. J Hypertens 23:779–784
Zigman JM, Jones JE, Lee CE, Saper CB, Elmquist JK (2006) Expression of ghrelin receptor mRNA in the rat and the mouse brain. J Comp Neurol 494:528–548
Acknowledgements
We thank Dr Kate Dziegielewska for the provision of anti-aquaporin 2 antibodies and Professor John Bertram for advice on the project and manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work utilised resources of the Australian Phenomics Network. It was supported by a grant from the National Health and Medical Research Council of Australia (grant number 1005811).
Rights and permissions
About this article
Cite this article
Venables, G., Hunne, B., Bron, R. et al. Ghrelin receptors are expressed by distal tubules of the mouse kidney. Cell Tissue Res 346, 135–139 (2011). https://doi.org/10.1007/s00441-011-1240-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-011-1240-4