Adenylyl cyclase 4 does not regulate collecting duct water and sodium handling

Kittikulsuth, Wararat; Stuart, Deborah; Kohan, Donald E.

doi:10.1002/phy2.277

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…1). AC6 is the principal AC mediating these responses, as only AC6-deficient mice have urine concentration defects (54,55,118,122). However, cAMP-independent mechanisms for AQP2 trafficking also exist, as previously demonstrated, e.g., stimulation of prostanoid receptors EP2 and EP4 and short-term exposure to peroxisomal proliferator-activated receptor subtype ␥-agonist (102,111).…”

Section: Vasopressin-regulated Aqp2mentioning

confidence: 80%

Molecular mechanisms regulating aquaporin-2 in kidney collecting duct

Jung

Kwon

2016

American Journal of Physiology-Renal Physiology

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The kidney collecting duct is an important renal tubular segment for regulation of body water homeostasis and urine concentration. Water reabsorption in the collecting duct principal cells is controlled by vasopressin, a peptide hormone that induces the osmotic water transport across the collecting duct epithelia through regulation of water channel proteins aquaporin-2 (AQP2) and aquaporin-3 (AQP3). In particular, vasopressin induces both intracellular translocation of AQP2-bearing vesicles to the apical plasma membrane and transcription of the Aqp2 gene to increase AQP2 protein abundance. The signaling pathways, including AQP2 phosphorylation, RhoA phosphorylation, intracellular calcium mobilization, and actin depolymerization, play a key role in the translocation of AQP2. This review summarizes recent data demonstrating the regulation of AQP2 as the underlying molecular mechanism for the homeostasis of water balance in the body.

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Section: Vasopressin-regulated Aqp2mentioning

confidence: 80%

Molecular mechanisms regulating aquaporin-2 in kidney collecting duct

Jung

Kwon

2016

American Journal of Physiology-Renal Physiology

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“…Previous studies have ruled out the involvement of AC3 and AC4 in the vasopressin-dependent stimulation of cAMP (21,22) and suggested that the most likely AC involved is AC6 (42), which is the most abundant AC in the CD. However, the present study did not allow defining which of the ACs is involved in the V2R-dependent stimulation of renin in the CD.…”

Section: Discussionmentioning

confidence: 99%

Vasopressin/V2 receptor stimulates renin synthesis in the collecting duct

González

Cifuentes-Araneda

Ibaceta-Gonzalez

et al. 2016

American Journal of Physiology-Renal Physiology

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Renin is synthesized in the principal cells of the collecting duct (CD), and its production is increased via cAMP in angiotensin (ANG) II-dependent hypertension, despite suppression of juxtaglomerular (JG) renin. Vasopressin, one of the effector hormones of the reninangiotensin system (RAS) via the type 2-receptor (V2R), activates the cAMP/PKA/cAMP response element-binding protein (CREB) pathway and aquaporin-2 expression in principal cells of the CD. Accordingly, we hypothesized that activation of V2R increases renin synthesis via PKA/CREB, independently of ANG II type 1 (AT1) receptor activation in CD cells. Desmopressin (DDAVP; 10 Ϫ6 M), a selective V2R agonist, increased renin mRNA (ϳ3-fold), prorenin (ϳ1.5-fold), and renin (ϳ2-fold) in cell lysates and cell culture media in the M-1 CD cell line. Cotreatment with DDAVPϩH89 (PKA inhibitor) or CREB short hairpin (sh) RNA prevented this response. H89 also blunted DDAVP-induced CREB phosphorylation and nuclear localization. In 48-h water-deprived (WD) mice, prorenin-renin protein levels were increased in the renal inner medulla (ϳ1.4-and 1.8-fold). In WD mice treated with an ACE inhibitor plus AT1 receptor blockade, renin mRNA and prorenin protein levels were still higher than controls, while renin protein content was not changed. In M-1 cells, ANG II or DDAVP increased prorenin-renin protein levels; however, there were no further increases by combined treatment. These results indicate that in the CD the activation of the V2R stimulates renin synthesis via the PKA/CREB pathway independently of RAS, suggesting a critical role for vasopressin in the regulation of renin in the CD.intrarenal renin-angiotensin system; collecting duct; water deprivation; distal tubular renin; prorenin; PKA/CREB THE RENIN-ANGIOTENSIN SYSTEM (RAS) plays a pivotal role in the regulation of blood pressure (BP) and in the maintenance of body sodium and fluid balance. There is growing evidence demonstrating the presence of the RAS in the tissues of renal and cardiovascular systems (5-7, 35), supporting the importance of the tissue RAS in the accomplishment of its functions. The kidneys generate angiotensin II (ANG II) de novo (46, 47). The luminal presence of angiotensinogen (AGT) in the proximal tubules (PT) (24), angiotensin-converting enzyme (ACE) in the collecting duct (CD) (3,15,25,39), and prorenin and renin in the distal nephron has been established (40, 41). These findings further support the formation of intratubular ANG II from sequential coordinated actions of tubular renin and ACE that act on AGT substrate delivered from the proximal segments. As evidence, ANG II, AGT, and renin contents are increased in the kidneys from ANG II-infused hypertensive rats (12), which contribute to sodium reabsorption (48). However, the mechanisms regulating renin in the CD and its physiological implications are not well understood.There is consensus evidence showing that the cAMP-PKA and cAMP response element-binding protein (CREB) pathway constitute the central pathway for renin regulation in JG ...

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“…A tissue-specific knockout of AC4 has been generated for loss of expression in kidney collecting duct principal cells. AC4 does not appear to play a role in water and sodium handling in kidney Pharmacological Modulation of Mammalian Adenylyl Cyclases (Kittikulsuth et al, 2014a). Phenotypes from other tissues have not yet been reported.…”

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confidence: 96%