Regulation of intracellular cAMP content in kidney tubules: role of adenylyl cyclases inhibitable by calcium
Chabardès, D.; Elalouf, J.M.; Aarab, L.
Nephrologie 20(4): 193-201
1999
ISSN/ISBN: 0250-4960 PMID: 10480151 Document Number: 498608
Adenylyl cyclase (AC) isoforms 5 and 6 can be inhibited by submicromolar concentrations of Ca2+. Quantitative RT-PCR allowed to study the corresponding messengers (mRNA) along the rat nephron. The results demonstrate a significant expression of AC 6 mRNA all along the nephron and of AC 5 mRNA in the glomerulus and the collecting tubule located in the cortex and the outer medulla. Regulation of cAMP synthesis and of intracellular cAMP content in defined renal cell types established the functional expression of AC 5 and AC 6. In particular, adenylyl cyclase activity is strongly stimulated by hormones and can be inhibited by several factors which either increase intracellular Ca2+ concentration or are coupled to G alpha 1. In each renal cell studied, the expression of 5 and 6 isoforms allow to integrate specific, multiple and independent inhibitory pathways which contribute to decrease intracellular cAMP content.