Glucagon-Sensitive Adenylate Cyclase in Human Renal Medulla

Mulvehill, John B.; Hui, Yvonne S.F.; Barnes, Larry D.; Palumbo, P. J.; Douša, Thomas P.

doi:10.1210/jcem-42-2-380

Cited by 23 publications

(11 citation statements)

References 12 publications

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“…3, age and cause ofdeath not indicated, storage, about 48 h; kidney No. 4, from a 53-year-old male who died of a brain hemorrhage, storage, 48 h; kidney No. 5, from a 48-year-old female, cause of death not indicated, storage about 12 h.…”

Section: Methodsmentioning

confidence: 99%

“…The protein content per millimeter of tubular length was calculated for the human segments, assuming the same value. Table VII In homogenates from normal human kidney tissue, basal AC activities ranging from 5 to 20 pmol/min -mg were reported for the cortex (5, 6) and from 7 to 12 pmol/min -mg for the medulla, depending on the conditions used by the different authors (3,4 The high AC sensitivity to low hormonal concentrations observed here, as well as the magnitude, specificity, and reproducibility of the stimulations obtained, suggest that the responsive segments (as revealed by this in vitro AC microassay) probably correspond to physiological target sites for the corresponding hormones in the living human kidney. As shown in Fig.…”

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confidence: 99%

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Adenylate cyclase responsiveness to hormones in various portions of the human nephron.

Chabardès¹,

Gagnan-Brunette²,

Imbert–Teboul³

et al. 1980

J. Clin. Invest.

154

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A B S T R A C T The action sites for parathyroid hormone (PTH), salmon calcifonin (SCT), and argininevasopressin (AVP) were investigated along the human nephron by measuring adenylate cyclase activity, using a single tubule in vitro microassay. Well-localized segments of tubule were isolated by microdissection from five human kidneys unsuitable for transplantation.PTH (10 IU/ml) increased adenylate cyclase activity in the convoluted and the straight proximal tubule, in the medullary and cortical portions of the thick ascending limb, and in the early portion of the distal convoluted tubule (corresponding stimulated:basal activity ratios were 64, 19, 10, 18, and 22, respectively).SCT (10 ng/ml) increased adenylate cyclase activity in the medullary and cortical portions of the thick ascending limb, in the early portion of the distal convoluted tubule, and, to a lesser extent, in the cortical and the medullary collecting tubule (activity ratios were 7, 14, 15, 3, and 3, respectively).AVP (1 ,tM) stimulated adenylate cyclase activity in the terminal nephron segments only, i.e., the late portion of the distal convoluted tubule, the cortical and medullary portions ofthe collecting tubule (activity ratios 81, 51, and 97, respectively).As measured in one experiment, nearly one-half maximal responses were obtained with 0.1 IU/ml PTH or 0.3 ng/ml SCT in thick ascending limbs and with 1 nM AVP in collecting tubules, suggesting that enzyme sensitivity to hormones was well preserved under the conditions used in this study.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Adenylate cyclase responsiveness to hormones in various portions of the human nephron.

Chabardès¹,

Gagnan-Brunette²,

Imbert–Teboul³

et al. 1980

J. Clin. Invest.

154

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“…Glucagon stimulates adenylate cyclase and cAMP production in nephrons and in cell-free preparations of human renal medullas (54,75). Although the role of glucagon in the control of renal glucose output remains uncertain, glucagon regulates the rate of kidney filtration, urea excretion, and water reabsorption by the kidney (26) via direct and indirect mechanisms (4).…”

Section: Glucagon the Kidney And The Gastrointestinal Tractmentioning

confidence: 99%

Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes

Ali¹,

Drucker²

2009

American Journal of Physiology-Endocrinology and Metabolism

115

136

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“…The first group shows the effect of 10 Ϫ7 M glucagon on Pf. This dose was chosen because it was the lowest dose that caused a reproducible effect, even though Di Stefano et al (13) In micropuncture and other studies, the dose used varied widely (7,8,12,13,15,18,19,28).…”

Section: Effect Of Glucagon On Water Reabsorptionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Yano¹,

Cesar²,

Araújo³

et al. 2009

American Journal of Physiology-Renal Physiology

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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...

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Glucagon-Sensitive Adenylate Cyclase in Human Renal Medulla

Cited by 23 publications

References 12 publications

Adenylate cyclase responsiveness to hormones in various portions of the human nephron.

Adenylate cyclase responsiveness to hormones in various portions of the human nephron.

Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes

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

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