Lack of intramembranous particle clusters in collecting ducts of mice with nephrogenic diabetes insipidus

Abstract

We suggested previously, on the basis of indirect evidence, that in two strains of mice with nephrogenic defects of urinary concentration the deficiency arose from an inadequate rise in water permeability of the collecting duct system. In this study we tested the question further by assuming that the frequency of intramembranous particle (IMP) clusters seen by freeze-fracture can be used as a morphological marker of vasopressin-induced water permeability. Three genotypes of mice were studied: 1) DI +/+ Severe, with florid, vasopressin-resistant diabetes insipidus; 2) DI +/+ Nonsevere, with an intermediate deficiency of urinary concentration; and 3) normal, VII +/+ mice. In addition, we examined a group of DI +/+ Severe mice that had been injected with exogenous 1-desamino-8-D-arginine vasopressin (DDAVP) subcutaneously for 3 days. Since the results in this group did not differ from those in untreated DI +/+ Severe mice, all data for this genotype were combined. IMP clusters within luminal membranes of inner medullary collecting duct principal cells were quantified by freeze-fracture electron microscopy. Urinary osmolality and percentage of cells showing clusters were, respectively: 203 +/- 43 mosmol/kg H2O and 0% in DI +/+ Severe mice; 1,133 +/- 86 and 33 +/- 4 in DI +/+ Nonsevere mice; and 2,234 +/- 190 and 52 +/- 5 in VII +/+ animals. With the exception of one animal, there was no overlap of the data, which were significantly different from one another for each variable. We conclude that in DI +/+ Severe mice, both endogenous and exogenous vasopressin are unable to increase the water permeability of medullary collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Apical membrane endocytosis via coated pits is stimulated by removal of antidiuretic hormone from isolated, perfused rabbit cortical collecting tubule

“…To conclude, this investigation extends the earlier observation [1,2] that ADH stimulation of rat collecting ducts causes the appearance of particle aggregates in apical membrane coated pits. Our studies are the first to demonstrate directly that increased apical membrane endocytosis occurs via coated pits in rabbit cortical collecting duct following removal of ADH from the peritubular bathing medium.…”

Aquaporin 2 (AQP2) and vasopressin type 2 receptor (V2R) endocytosis in kidney epithelial cells: AQP2 is located in ‘endocytosis‐resistant’ membrane domains after vasopressin treatment

“…However, the fact that many apical FITC‐positive vesicles were unstained for AQP2 indicates that at least a portion of the apical AQP2 in these cells is able to escape endocytosis and remain at the cell surface. The amount of apical endocytosis and the degree of co‐localization with AQP2 was variable from cell to cell, indicating a cellular heterogeneity in the water permeability response of principal cells that has been suggested previously based on freeze‐fracture studies (Brown et al, 1985). This implies that, under conditions of ad lib .…”

Transepithelial water flow regulates apical membrane retrieval in antidiuretic hormone-stimulated toad urinary bladder.

“…1 shows the osmotic water flow across bladders that were stimulated with ADH in the absence ofan osmotic gradient, followed by imposition ofdifferent hypotonic mucosal solutions to produce a series of transepithelial osmotic gradients. In those bladders subjected to large osmotic gradients, the initial 12 high rate of water flow was rapidly attenuated. As anticipated, those bladders exposed to smaller osmotic gradients had a proportionally lower initial rate of ADH-stimulated water flow.…”

“…A large body of evidence indicates that particle aggregates are closely correlated with or are themselves water channels responsible for the increase in apical membrane water permeability induced by ADH (reviews 8, 9). Freeze-fracture electron microscopy has also revealed that distinctive intramembrane particle structures are closely correlated with ADHinduced permeability changes in the apical membrane of the mammalian collecting duct (10)(11)(12).…”