title: β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function.
abstract: To date, the study of the sympathetic regulation of renal function has been restricted to the important contribution of β1- and β2-adrenergic receptors (ARs). Here we investigate the expression and the possible physiologic role of β3-adrenergic receptor (β3-AR) in mouse kidney. The β3-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 β3-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 β3-AR antagonist L748,337 or by the protein kinase A inhibitor H89. Interestingly, genetic inactivation of β3-AR in mice was associated with significantly increased urine excretion of water, sodium, potassium, and chloride. Stimulation of β3-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 β3-AR stimulation in the kidney. Hence, β3-AR agonism might be useful to bypass AVPR2-inactivating mutations.
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy. Electronic address: giuseppe.procino@uniba.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procino
authors.affiliation: Department of Sciences, University of Basilicata, Potenza, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Carmosino
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Milano
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Dal Monte
authors.affiliation: Department of Sciences, University of Basilicata, Potenza, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Schena
authors.affiliation: Department of Biology, University of Bari, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Mastrodonato
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gerbino
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bagnoli
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy; Institute of Biomembranes and Bioenergetics, National Research Council, Bari, Italy; National Institute of Biostructures and Biosystems (INBB), Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Svelto
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000627:Aminophenols / Q000494:pharmacology; D051399:Aquaporin 2 / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004573:Electrolytes / Q000652:urine; D004983:Ethanolamines / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005919:Glomerular Filtration Rate / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D007684:Kidney Tubules / Q000378:metabolism / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000502:physiology; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism; D065667:Renal Elimination / Q000502:physiology; D064466:Solute Carrier Family 12, Member 1 / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000627:Aminophenols; C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; C057368:BRL 37344; D000242:Cyclic AMP; D004573:Electrolytes; D004983:Ethanolamines; D007546:Isoquinolines; C120576:L 748,337; D022702:Receptors, Adrenergic, beta-3; D017483:Receptors, Vasopressin; C578715:Slc12a1 protein, mouse; D064466:Solute Carrier Family 12, Member 1; D013449:Sulfonamides; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: AQP2; NKCC2; antidiuresis; vasopressin; β(3) adrenergic receptors