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

J Clin Invest. 1996 Nov 15;98(10):2251-8. doi: 10.1172/JCI119035.


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 x 100 grams of body weight [BW]) or urea (2.5 micromol/min x 100 grams BW) was infused intravenously for 200 min with or without G (1.2 ng/min x 100 grams BW, a physiological dose which, alone, does not influence PTR or GFR). cAMP increased markedly the excretion of phosphate and sodium (+303 and +221%, respectively, P < 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 < 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / pharmacology
  • Cyclic AMP / blood
  • Cyclic AMP / pharmacology*
  • Cyclic AMP / physiology*
  • Glucagon / pharmacology*
  • Kidney / physiology*
  • Kidney Concentrating Ability / physiology*
  • Male
  • Natriuresis / physiology*
  • Phosphates / metabolism
  • Rats
  • Rats, Wistar
  • Renal Agents / pharmacology
  • Urea / blood
  • Urea / pharmacology*
  • Water / metabolism


  • Phosphates
  • Renal Agents
  • Water
  • Arginine Vasopressin
  • Urea
  • Glucagon
  • Cyclic AMP