| First Author | Poulsen SB | Year | 2018 |
| Journal | Clin Sci (Lond) | Volume | 132 |
| Issue | 16 | Pages | 1779-1796 |
| PubMed ID | 29941522 | Mgi Jnum | J:324562 |
| Mgi Id | MGI:6859836 | Doi | 10.1042/CS20180060 |
| Citation | Poulsen SB, et al. (2018) Adenylyl cyclase 6 is required for maintaining acid-base homeostasis. Clin Sci (Lond) 132(16):1779-1796 |
| abstractText | Adenylyl cyclase (AC) isoform 6 (AC6) is highly expressed throughout the renal tubule and collecting duct (CD), catalyzes the synthesis of cAMP and contributes to various aspects of renal transport. Several proteins involved in acid-base homeostasis are regulated by cAMP. In the present study, we assess the relative contribution of AC6 to overall acid-base regulation using mice with global deletion of AC6 (AC6(-/-)) or newly generated mice lacking AC6 in the renal tubule and CD (AC6(loxloxPax8Cre)). Higher energy expenditure in AC6(-/-) relative to wild-type (WT) mice, was associated with lower urinary pH, mild alkalosis in conjunction with elevated blood HCO3(-) concentrations, and significantly higher renal abundance of the H(+)-ATPase B1 subunit. In contrast with WT mice, AC6(-/-) mice have a less pronounced increase in urinary pH after 8 days of HCO3(-) challenge, which is associated with increased blood pH and HCO3(-) concentrations. Immunohistochemistry demonstrated that AC6 was expressed in intercalated cells (IC), but subcellular distribution of the H(+)-ATPase B1 subunit, pendrin, and the anion exchangers 1 and 2 in AC6(-/-) mice was normal. In the AC6(-/-) mice, H(+)-ATPase B1 subunit levels after HCO3(-) challenge were greater, which correlated with a higher number of type A IC. In contrast with the AC6(-/-) mice, AC6(loxloxPax8Cre) mice had normal urinary pH under baseline conditions but higher blood HCO3(-) than controls after HCO3(-) challenge. In conclusion, AC6 is required for maintaining normal acid-base homeostasis and energy expenditure. Under baseline conditions, renal AC6 is redundant for acid-base balance but becomes important under alkaline conditions. |
