Impaired urinary concentration after vasopressin and its gradual correction in hypothalamic diabetes insipidus

Harrington, Avery R.; Valtin, Heinz

doi:10.1172/jci105746

Cited by 87 publications

(33 citation statements)

References 24 publications

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“…This suggests an asymmetrical transmembrane rearrangement of AQP4 molecules that at present is of uncertain functional relevance. The fact that a similar arrangement was not seen after acute (several hours) dDAVP exposure implies that the rearrangement might not be a direct effect of the hormone, but might result from a progressive increase in interstitial osmolality that occurs in dDAVP-treated Brattleboro rats (12).…”

Section: Discussionmentioning

confidence: 97%

Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells

Silberstein¹,

Bouley²,

Huang³

et al. 2004

American Journal of Physiology-Renal Physiology

142

145

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(AQP4) water channels exist as heterotetramers of M1 and M23 splice variants and appear to be present in orthogonal arrays of intramembraneous particles (OAPs) visualized by freeze-fracture microscopy. We report that AQP4 forms OAPs in rat gastric parietal cells but not in parietal cells from the mouse or kangaroo rat. Furthermore, the organization of principal cell OAPs in Brattleboro rat kidney is perturbed by vasopressin (arginine vasopressin). Membranes of LLC-PK1 cells expressing M23-AQP4 showed large, abundant OAPs, but none were detectable in cells expressing M1-AQP4. Measurements of osmotic swelling of transfected LLC-PK1 cells using videomicroscopy, gave osmotic water permeability coefficient (Pf) values (in cm/s) of 0.018 (M1-AQP4), 0.019 (M23-AQP4), and 0.003 (control). Quantitative immunoblot and immunofluorescence showed an eightfold greater expression of M1-over M23-AQP4 in the cell lines, suggesting that single-channel pf (cm 3 /s) is much greater for the M23 variant. Somatic fusion of M1-and M23-AQP4 cells (Pf ϭ 0.028 cm/s) yielded OAPs that were fewer and smaller than in M23 cells alone, and M1-to-M23 expression ratios (ϳ1:4) normalized to AQP4 in M1 or M23 cells indicated a reduced single-channel pf for the M23 variant. Expression of an M23-AQP4-Ser 111E mutant produced ϳ1.5-fold greater single-channel pf and OAPs that were up to 2.5-fold larger than wild-type M23-AQP4 OAPs, suggesting that a putative PKA phosphorylation site Ser 111 is involved in OAP formation. We conclude that the higher-order organization of AQP4 in OAPs increases single-channel osmotic water permeability by one order of magnitude and that differential cellular expression levels of the two isoforms could regulate this organization. water transport; freeze-fracture; LLC-PK1 cells; orthogonal arrays; intramembraneous particles THE MAMMALIAN FAMILY OF AQUAPORIN water channels consists of 12 known members, each with a specific tissue distribution and membrane localization pattern. However, the role of aquaporin-4 (AQP4) in water transport physiology is not well understood. AQP4 was the first aquaporin to be observed and identified in biological membranes, because when examined by freeze-fracture electron microscopy, it forms characteristic arrays of intramembraneous particles (IMPs) in the form of checkerboard aggregates or orthogonal arrays of intramembraneous particles (OAPs). These OAPs were described in various cell membranes long before a role in water permeability was suspected (3,18,27,31,32). The relationship of OAPs to water channels was first suggested by earlier studies showing that membranes that contained OAPs, including astrocytes, gastric parietal cells, and collecting duct principal cells were immunostained by an antibody raised against the whole AQP1 (then called CHIP28) protein (37). A different antibody raised against skeletal muscle OAP-containing membranes also recognized an ϳ30-kDa protein in these membranes (15,41). In this way, a protein initially called basolateral intrinsic membrane protein (BLIP) was ...

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Section: Discussionmentioning

confidence: 97%

Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells

Silberstein¹,

Bouley²,

Huang³

et al. 2004

American Journal of Physiology-Renal Physiology

142

145

View full text Add to dashboard Cite

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“…Apparently the reduction of the poly(A) tail length can modulate the efficiency of the overall process of RNA accumulation, transport, and expression. It has been demonstrated (23,24) that due to the lack of an existing osmotic medullary gradient in the Brattleboro rat's renal papilla, the AVP-treated animal is initially unable to concentrate its urine above 600 mosM, even with a very high concentration of AVP, far below the 1200 mosM lowest value of a normal rat. An explanation of the discrepancy between AVP levels and urine osmolarity could be that, with the increase in intracellular salt concentration in the tubules, the animal becomes more responsive to circulating AVP.…”

Section: Discussionmentioning

confidence: 99%

Reduction of exogenous vasopressin RNA poly(A) tail length increases its effectiveness in transiently correcting diabetes insipidus in the Brattleboro rat.

Maciejewski-Lenoir

Jirikowski

Sanna

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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Magnocellular hypothalamic neurons in Brattleboro rats can accumulate, transport, and translate exogenous [ArgeJvasopressin (AVP) mRNA after injection in the hypothalamo-hypophysial tract in amounts sufficient to reverse transiently the animals' characteristic diabetes insipidus. In the present study, different preparations of hypothalamic RNA extracted from normal rats or synthetic AVP RNA were injected into the lateral hypothalamus ofBrattleboro rats. Poly(A)-RNA and poly(A)+ RNA from which tails were removed by RNase H digestion were much more effective than poly(A)+ RNA in expressing AVP in the magnocellular hypothalamic neurons and in raising urine osmolarity. Synthetic AVP RNA lacking a poly(A) tail also produced a very potent dose-dependent diabetes insipidus reversal. Our results suggest that a short or absent poly(A) tail may facilitate the accumulation, transport, or expression of exogenous AVP mRNA by magnoceilular neurons.We previously reported that oxytocin mRNA can be found associated with the secretory vesicles within the axonal compartment of rat hypothalamo-neurohypophysial system neurons (1).[Arg8]Vasopressin (AVP) mRNA has also been found in the axonal compartment by several investigators (2-7). Previous studies indicate that the length of total hypothalamic AVP mRNA poly(A) tail is increased from 250 to 400 nucleotides following a hyperosmotic stimulus (8). Structural changes in the AVP mRNA have also been found to be associated with its translocation; using osmotically challenged rats, Mohr et al. (9) have shown that the poly(A) tail length of AVP mRNA is progressively shortened during axonal transport in the hypothalamo-neurohypophysial tract and is virtually nonexistent by the time it reaches the posterior lobe.More recently, we have studied the functional significance of the intraaxonal mRNA by experiments with the Brattleboro rat. This naturally occurring mutant rat, with a single base deletion in exon B of the propressophysin gene (10), is unable to translate functional AVP and has chronic diabetes insipidus, a condition characterized by the inability to concentrate urine. When total RNA extracted from the hypothalami of osmotically challenged normal rats was microinjected into the hypothalamo-neurohypophysial tract of homozygous Brattleboro rats, AVP mRNA was accumulated by magnocellular neurons, transported, and translated into immunoreactive vasopressin (11). Exogenous mRNA from normal rats and synthetic AVP RNA were both capable of causing a temporary correction of diabetes insipidus as well as production of significant plasma levels of immunoreactive AVP. Control injections with total RNA extracted from the cortex or hypothalamic RNA digested with RNase, as well as injections with the sense RNA probe into the lateral ventricle or into the cerebral cortex, were all ineffective in changing urine osmolarity or vasopressin levels.In an effort to increase the concentration of specific AVP mRNA in the RNA extract, we initially sought to enrich the polyadenylylated fraction by pas...

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“…The Journal of Clinical Investigation Volume 54 August 1974-252-262 In the present study, colchicine and vinblastine, two microtubule-disrupting agents (8) shown to elicit supramaximal antidiuretic effect in rats (9). Lumicolchicine was prepared by irradiation of colchicine with a long wavelength ultraviolet lamp as described by Mizel and Wilson (10 (Tables I and III Additional experiments were conducted to test for nonspecific toxic effects of colchicine.…”

Section: Introductionmentioning

confidence: 99%

Effects of Colchicine and Vinblastine on the Cellular Action of Vasopressin in Mammalian Kidney A POSSIBLE ROLE OF MICROTUBULES

Douša¹,

Barnes²

1974

J. Clin. Invest.

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Impaired urinary concentration after vasopressin and its gradual correction in hypothalamic diabetes insipidus

Cited by 87 publications

References 24 publications

Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells

Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells

Reduction of exogenous vasopressin RNA poly(A) tail length increases its effectiveness in transiently correcting diabetes insipidus in the Brattleboro rat.

Effects of Colchicine and Vinblastine on the Cellular Action of Vasopressin in Mammalian Kidney A POSSIBLE ROLE OF MICROTUBULES

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