Role of adenosine on glucagon-induced cAMP in a human cortical collecting duct cell line

• Published in: Kidney international Vol. 47; no. 5; pp. 1310 - 1318
• Main Authors: Prié, Dominique, Friedlander, Gérard, Coureau, Christiane, Vandewalle, Alain, Cassingéna, Roland, Ronco, Pierre M.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01-05-1995; Nature Publishing
• Subjects: Adenosine - physiology; Analysis of Variance; Animals; Atrial Natriuretic Factor - pharmacology; Biological and medical sciences; Calcium - metabolism; Cell Line; Cyclic AMP - biosynthesis; Cyclic GMP - biosynthesis; Fundamental and applied biological sciences. Psychology; Glucagon - pharmacology; Humans; Intracellular Fluid - drug effects; Intracellular Fluid - metabolism; Kidney Tubules, Collecting - drug effects; Kidney Tubules, Collecting - immunology; Kidney Tubules, Collecting - metabolism; Rabbits; Rats; Receptors, Purinergic P1 - metabolism; Vasopressins - pharmacology; Vertebrates: urinary system; Human; Pancreatic hormone; Adenosine; Glucagon; Interaction; Cyclic AMP; Atrial natriuretic peptide; Kidney; Signal transduction; Regulation(control); Cell line; Urinary system; Bradykinin; Angiotensin; Second messenger; Nucleoside; Epithelial cell; Collecting duct; Adenosine receptor; Renal cortex
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.1995.186

Role of adenosine on glucagon-induced cAMP in a human cortical collecting duct cell line. The hormonal responsiveness profile of the cortical collecting duct varies from one species to another. To identify the hormones and agonists that modulate the functions of this tubule segment in the human species, we generated a cell line (HCD) immortalized by SV40 virus. The tubular origin of this cell line was assessed by the expression of collecting duct-specific antigens and the ability of vasopressin to increase by nine-fold cAMP synthesis. Glucagon and adenosine stimulated cAMP synthesis, and atrial natriuretic peptide stimulated cGMP synthesis in a concentration-dependent manner. Bradykinin, adenosine and angiotensin increased intracellular calcium concentration ([Ca2+]i). Because adenosine can regulate tubular functions, we examined its role on glucagon-induced cAMP synthesis. Using adenosine analogs, we demonstrated that HCT cells both expressed adenosine type-2 (A2) receptors which stimulated cAMP production, and adenosine type-1 (A1) receptors linked to [Ca2+]i increase which inhibited glucagon-stimulated cAMP synthesis. The inhibitory effect was abolished by pertussis toxin, and was neither due to [Ca2+]i increase nor to protein kinase C activation, which indicated that some A1 adenosine receptors were directly negatively coupled to adenylyl cyclase. These results suggest that adenosine can modify human cortical collecting duct functions in opposite ways according to the adenosine receptor activated.