| First Author | Procino G | Year | 2016 |
| Journal | Kidney Int | Volume | 90 |
| Issue | 3 | Pages | 555-67 |
| PubMed ID | 27206969 | Mgi Jnum | J:323074 |
| Mgi Id | MGI:6835388 | Doi | 10.1016/j.kint.2016.03.020 |
| Citation | Procino G, et al. (2016) beta3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function. Kidney Int 90(3):555-67 |
| abstractText | To date, the study of the sympathetic regulation of renal function has been restricted to the important contribution of beta1- and beta2-adrenergic receptors (ARs). Here we investigate the expression and the possible physiologic role of beta3-adrenergic receptor (beta3-AR) in mouse kidney. The beta3-AR is expressed in most of the nephron segments that also express the type 2 vasopressin receptor (AVPR2), including the thick ascending limb and the cortical and outer medullary collecting duct. Ex vivo experiments in mouse kidney tubules showed that beta3-AR stimulation with the selective agonist BRL37344 increased intracellular cAMP levels and promoted 2 key processes in the urine concentrating mechanism. These are accumulation of the water channel aquaporin 2 at the apical plasma membrane in the collecting duct and activation of the Na-K-2Cl symporter in the thick ascending limb. Both effects were prevented by the beta3-AR antagonist L748,337 or by the protein kinase A inhibitor H89. Interestingly, genetic inactivation of beta3-AR in mice was associated with significantly increased urine excretion of water, sodium, potassium, and chloride. Stimulation of beta3-AR significantly reduced urine excretion of water and the same electrolytes. Moreover, BRL37344 promoted a potent antidiuretic effect in AVPR2-null mice. Thus, our findings are of potential physiologic importance as they uncover the antidiuretic effect of beta3-AR stimulation in the kidney. Hence, beta3-AR agonism might be useful to bypass AVPR2-inactivating mutations. |
