Cyclic AMP is a hepatorenal link influencing natriuresis and contributing to glucagon-induced hyperfiltration in rats.

Abstract

The effects of glucagon (G) on proximal tubule reabsorption (PTR) and GFR seem to depend on a prior action of this hormone on the liver resulting in the liberation of a mediator and/or of a compound derived from amino acid metabolism. This study investigates in anesthetized rats the possible contribution of cAMP and urea, alone and in combination with a low dose of G, on phosphate excretion (known to depend mostly on PTR) and GFR. After a 60-min control period, cAMP (5 nmol/min ϫ 100 grams of body weight [BW]) or urea (2.5 mol/min ϫ 100 grams BW) was infused intravenously for 200 min with or without G (1.2 ng/min ϫ 100 grams BW, a physiological dose which, alone, does not influence PTR or GFR). cAMP increased markedly the excretion of phosphate and sodium ( ϩ 303 and ϩ 221%, respectively, P Ͻ 0.01 for each) but did not alter GFR. Coinfusion of cAMP and G induced the same tubular effects but also induced a 20% rise in GFR ( P Ͻ 0.05). Infusion of urea, with or without G, did not induce significant effects on PTR or GFR. After G infusion at increasing doses, the increase in fractional excretion of phosphate was correlated with a simultaneous rise in plasma cAMP concentration and reached a maximum for doubling of plasma cAMP. These results suggest that cAMP, normally released by the liver into the blood under the action of G, ( a ) is probably an essential hepatorenal link regulating the intensity of PTR, and ( b ) contributes, in conjunction with specific effects of G on the nephron, to the regulation of GFR. ( J. Clin. Invest. 1996. 98: 2251-2258.)

The cyclic AMP phenotype of fragile X and autism

“…Increased plasma cyclic AMP levels in autism are significantly and positively associated with hyperkinesia and serum serotonin levels (Hoshino, Kumashiro et al 1979). However, since a variety of tissues contribute to plasma cAMP levels, the interpretation of plasma cAMP studies is not specific to brain (Goldberg 1984) and could be explained by alternative pathways such as hepatorenal plasma cAMP signaling (Ahloulay, Dechaux et al 1996). Although CSF and peripheral blood measures indicate that cAMP levels are normal to high in autism, the cAMP cascade remains to be studied in the autistic brain.…”

Glucagon Receptor–Mediated Extracellular Signal–Regulated Kinase 1/2 Phosphorylation in Rat Mesangial Cells

“…The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (1 mmol/L) was added to all of the samples to prevent cAMP degradation. [17][18][19] After treatment, the medium was removed, and the cells were washed and lysed with 0.1 N HCl. The lysates were centrifuged at 1000g, and cAMP levels in supernatants were determined using a sensitive cAMP ELISA kit (R&D).…”

Cross-talk between angiotensin II and glucagon receptor signaling mediates phosphorylation of mitogen-activated protein kinases ERK 1/2 in rat glomerular mesangial cells

“…Animal and clinical studies have shown that hyperglucagonemia plays an important role in the development of glomerular hyperfiltration and mesangial cell injury [4][5][6]29]. In rats, we found that glomerular hyperfiltration induced by glucagon was attenuated by inhibiting angiotensinconverting enzyme (ACE) with enalapril [30,31], together suggesting that glucagon interacts with Ang II to regulate glomerular filtration.…”