Aquaporin 2 expression increased by glucagon in normal rat inner medullary collecting ducts

Abstract

LC, Magaldi AJ. Aquaporin 2 expression increased by glucagon in normal rat inner medullary collecting ducts. Am J Physiol Renal Physiol 296: F54 -F59, 2009. First published October 1, 2008 doi:10.1152/ajprenal.90367.2008.-It is well known that Glucagon (Gl) is released after a high protein diet and participates in water excretion by the kidney, principally after a protein meal. To study this effect in in vitro perfused inner medullary collecting ducts (IMCD), the osmotic water permeability (Pf; m/s) at 37°C and pH 7.4 in normal rat IMCDs (n ϭ 36) perfused with Ringer/HCO 3 was determined. Gl (10 Ϫ7 M) in absence of Vasopressin (AVP) enhanced the Pf from 4.38 Ϯ 1.40 to 11.16 Ϯ 1.44 m/s (P Ͻ 0.01). Adding 10 Ϫ8 , 10 Ϫ7 , and 10 Ϫ6 M Gl, the Pf responded in a dose-dependent manner. The protein kinase A inhibitor H8 blocked the Gl effect. The specific Gl inhibitor, des-His 1 -[Glu 9 ] glucagon (10 Ϫ7 M), blocked the Glstimulated Pf but not the AVP-stimulated Pf. There occurred a partial additional effect between Gl and AVP. The cAMP level was enhanced from the control 1.24 Ϯ 0.39 to 59.70 Ϯ 15.18 fm/mg prot after Gl 10 Ϫ7 M in an IMCD cell suspension. The immunoblotting studies indicated an increase in AQP2 protein abundance of 27% (cont 100.0 Ϯ 3.9 vs. Gl 127.53; P ϭ 0.0035) in membrane fractions extracted from IMCD tubule suspension, incubated with 10 Ϫ6 M Gl. Our data showed that 1) Gl increased water absorption in a dosedependent manner; 2) the anti-Gl blocked the action of Gl but not the action of AVP; 3) Gl stimulated the cAMP generation; 4) Gl increased the AQP2 water channel protein expression, leading us to conclude that Gl controls water absorption by utilizing a Gl receptor, rather than a AVP receptor, increasing the AQP2 protein expression. glucagon; aquaporin 2; water transport; glucagon antagonist; vasopressin GLUCAGON IS A POLYPEPTIDE whose major physiological role is to participate in the regulation of blood sugar levels. Its action is mainly on hepatic glycogenolysis and gluconeogenesis. Even though the kidney is not considered to be the principal target organ for the action of glucagon, it has been known since 1957 (22) that this hormone enhances sodium excretion after intravenous administration to dogs. Other investigators have confirmed the natriuretic effect of glucagon by using different doses (9, 18, 19). In 1958, Sutherland et al. (23) showed that glucagon was able to produce glycogen breakdown in hepatocytes by stimulating adenylyl cyclase and cyclic adenosine monophosphate (cAMP).In 1976, Mulvehill et al. (15) demonstrated that glucagon produced a dose-dependent stimulation of adenylyl cyclase in cell-free preparations of human renal medullas. This finding showed that the effect of glucagon could be mediated by cAMP. In the 1980s, Bailly et al. (4), by measuring glucagonsensitive adenylyl cyclase activity, showed that distal nephrons are highly responsive to this hormone, and Butlen et al. (7), using [125 I]glucagon, showed that the nephron has a specific receptor for glucagon. On the ot...

Calcitonin Has a Vasopressin-like Effect on Aquaporin-2 Trafficking and Urinary Concentration

“…Interestingly, another G-proteincoupled receptor ligand, glucagon, also has antidiuretic effects, although its effect on AQP2 trafficking in vivo remains to be determined. 41,61 As expected from the distribution of CT receptors along the urinary tubule, 37,40 the effect of CT on AQP2 membrane accumulation was region-dependent. The effect was greater in the connecting segment and cortical collecting duct, where CT receptors are most abundant, than in the medullary collecting duct.…”

Glucagon induces the gene expression of aquaporin-8 but not that of aquaporin-9 water channels in the rat hepatocyte

“…5) suggests that a glucagon-induced AQP8 upregulation by decreased rate of calpain-mediated proteolysis is conceivable. Although this issue requires further investigation, it is interesting to point out that the protein expression of another member of the AQP family, i.e., renal AQP2, has been recently found to be induced by glucagon (53) and that this AQP also undergoes degradation by calpains (42).…”

Nutrient regulation of glucagon secretion: involvement in metabolism and diabetes

“…Kidneys are also a target site for glucagon, since its intravenous infusion is related to changes produced in urea synthesis and excretion as well as in water conservation ( 157 ) . In in vitro perfused inner medullary collecting ducts, glucagon induces cAMP production and changes in aquaporin 2 expression that affect water excretion ( 158 ) . Glucagon is also used as an anti-peristaltic agent because of its effects on small intestine motility ( 159 , 160 ) .…”