Extracellular cAMP inhibits proximal reabsorption

Are plasma membrane cAMP receptors involved?

Lise Bankir, Mina Ahloulay, Peter N Devreotes, Carole A. Parent

Research output: Contribution to journalArticle

Abstract

Glucagon binding to hepatocytes has been known for a long time to not only stimulate intracellular cAMP accumulation but also, intriguingly, induce a significant release of liver-borne cAMP in the blood. Recent experiments have shown that the well-documented but ill-understood natriuretic and phosphaturic actions of glucagon are actually mediated by this extracellular cAMP, which inhibits the reabsorption of sodium and phosphate in the renal proximal tubule. The existence of this "pancreato-hepatorenal cascade" indicates that proximal tubular reabsorption is permanently influenced by extracellular cAMP, the concentration of which is most probably largely dependent on the insulin-to-glucagon ratio. The possibility that renal cAMP receptors may be involved in this process is supported by the fact that cAMP has been shown to bind to brush-border membrane vesicles. In other cell types (i.e., adipocytes, erythrocytes, glial cells, cardiomyocytes), cAMP eggress and/or cAMP binding have also been shown to occur, suggesting additional paracrine effects of this nucleotide. Although not yet identified in mammals, cAMP receptors (cARs) are already well characterized in lower eukaryotes. The amoeba Dictyostelium discoideum expresses four different cARs during its development into a multicellular organism. cARs belong to the superfamily of seven transmembrane domain G protein-coupled receptors and exhibit a modest homology with the secretin receptor family (which includes PTH receptors). However, the existence of specific cAMP receptors in mammals remains to be demonstrated. Disturbances in the pancreato-hepatorenal cascade provide an adequate pathophysiological understanding of several unexplained observations, including the association of hyperinsulinemia and hypertension, the hepatorenal syndrome, and the hyperfiltration of diabetes mellitus. The observations reviewed in this paper show that cAMP should no longer be regarded only as an intracellular second messenger but also as a first messenger responsible for coordinated hepatorenal functions, and possibly for paracrine regulations in several other tissues.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number3 51-3
StatePublished - 2002

Fingerprint

Cyclic AMP Receptors
Cell Membrane
Glucagon
Mammals
Hepatorenal Syndrome
Proximal Kidney Tubule
Amoeba
Dictyostelium
Hyperinsulinism
Second Messenger Systems
Microvilli
Eukaryota
Adipocytes
Cardiac Myocytes
Neuroglia
Hepatocytes
Diabetes Mellitus
Nucleotides
Erythrocytes
Insulin

Keywords

  • Adipose tissue
  • Diabetes mellitus
  • Dictyostelium discoideum
  • Epinephrine
  • Glucagon
  • Hepatorenal syndrome
  • Hypertension
  • Insulin
  • Liver
  • Parathyroid hormone
  • Phosphate
  • Sodium

ASJC Scopus subject areas

  • Physiology

Cite this

Extracellular cAMP inhibits proximal reabsorption : Are plasma membrane cAMP receptors involved? / Bankir, Lise; Ahloulay, Mina; Devreotes, Peter N; Parent, Carole A.

In: American Journal of Physiology - Renal Physiology, Vol. 282, No. 3 51-3, 2002.

Research output: Contribution to journalArticle

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