Key result
Both DDAVP and DB-cAMP significantly increased water permeability of OMCD principal cells, with DB-cAMP increasing AQP2 but not AQP3 content in the membrane fraction.
Why the study?
The study investigated the role of cAMP in vasopressin-dependent regulation of apical and basolateral membrane water permeability in outer medullary collecting duct principal cells of Brattleboro rats.
In Brattleboro rats, AQP3-mediated water transport across the basolateral membrane of OMCD principal cells is likely regulated by ADH through both cAMP-dependent and other secondary messenger systems.
cAMP increases apical/basolateral water permeability in Brattleboro OMCD but not AQP3 levels; leaves open cAMP-independent pathways for vasopressin action in diabetes insipidus models.
Vasopressin (antidiuretic hormone, ADH) plays an important role in the regulation of water–salt balance in mammals. Brattleboro rats lack endogenous ADH due to a mutation in the ADH-neurophysin gene, leading to a recessive form of central diabetes insipidus. This work investigated the role of cAMP in ADH-dependent regulation of water permeability of the apical and basolateral membranes in outer medullary collecting duct (OMCD) principal cells in Brattleboro rats. Data obtained from water-loaded Wistar rats were used as a control. The osmotic water permeability coefficient (P f) of principal cells in isolated OMCD was assessed using a method based on calcein fluorescence quenching by cytoplasmic proteins. The content of aquaporins AQP2 and AQP3 in the membrane fraction of outer medullary cells was evaluated by Western blotting. Both the vasopressin V2 receptor agonist (DDAVP, 10–8 M) and the cell-permeable cAMP analog (DB-cAMP, 10–5 M) significantly increased the water permeability of both the apical and basolateral membranes of OMCD principal cells in both rat strains after a 25-min exposure, with the cAMP analog having a more pronounced effect compared to DDAVP. We have previously shown that short-term exposure to DDAVP increased AQP2 content in the membrane fraction of Wistar rats and AQP2-3 content in Brattleboro rats. In this study, Western blotting demonstrated that DB-cAMP increased the content of AQP2, but not AQP3, in the membrane fraction of the renal outer medulla in both Wistar and Brattleboro rats. It can be assumed that in Brattleboro rats, AQP3-mediated water transport across the basolateral membrane of OMCD principal cells is regulated by ADH not only through a cAMP-dependent pathway but also with the involvement of other, including calcium-related, secondary messenger systems.
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Батурина et al. (2025) studied Central diabetes insipidus. DDAVP and DB-cAMP vs. Control (water-loaded Wistar rats) was evaluated on Osmotic water permeability coefficient and AQP2/AQP3 content. Both DDAVP and DB-cAMP significantly increased water permeability of OMCD principal cells, with DB-cAMP increasing AQP2 but not AQP3 content in the membrane fraction.
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