Plasma cAMP: a hepatorenal link influencing proximal reabsorption and renal hemodynamics?
The existence of a hepatorenal link is suggested by several pathophysiological observations (indirect actions of glucagon on the kidney, hepatorenal syndrome), but the nature of this link remains unidentified. We propose that extracellular circulating cyclic AMP could be this link. Cyclic AMP (cAMP) is the intracellular second messenger of glucagon (G) action in the liver, and this organ is known to release cAMP in the blood in relatively large amounts after G administration. On the other hand, the proximal tubule (mainly the pars recta) is known to take up cAMP through the organic acid transport system. We observed that the glucagon-induced rise in phosphate excretion, which requires supraphysiologic concentration of G, was significantly correlated with the simultaneous rise in plasma cAMP and could be mimiked by i.v. infusion of cAMP alone. Moreover, we showed that a significant hyperfiltration (similar to that induced by supraphysiologic G) can be observed if cAMP (mimicking G-induced hepatic release) is coinfused with a much lower, physiologic, amount of G. Taken together, these observations suggest that: (1) cAMP is a hepatorenal link and that plasma cAMP permanently influences the intensity of reabsorption in the pars recta of the proximal tubule; and (2) that cAMP participates, in conjunction with G, to control GFR. Insulin is known to exert an inhibitory influence on G-induced cAMP release by the liver and will thus weaken the indirect (cAMP-mediated) influence of G on renal function. This "pancreato-hepatorenal cascade" may explain the natriuretic effects of G and antinatriuretic effects of insulin, and probably contributes to disturbances observed in some pathophysiological situations such as the edema of liver cirrhosis or hyperfiltration of diabetes.
Bankir
L
L
INSERM Unité 90, Hôpital Necker-Enfants Malades, Paris, France. bankir@citi2.fr
Martin
H
H
Déchaux
M
M
Ahloulay
M
M
D000042:Absorption; D000818:Animals; D000242:Cyclic AMP / Q000097:blood*; D006439:Hemodynamics; D006530:Hepatorenal Syndrome / Q000209:etiology; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008099:Liver / Q000502:physiology*; D009318:Natriuresis
D000242:Cyclic AMP