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Ohta E, Itoh T, Nemoto T, Kumagai J, Ko SB, Ishibashi K, Ohno M, Uchida K, Ohta A, Sohara R, Uchida S, Sasaki S, Rai T. pancreas-specific aquaporin 12 null mice showed increased susceptibility to caerulein-induced acute pancreatitis. Am J Physiol Cell Physiol 297: C1368-C1378, 2009. First published September 2, 2009; doi: 10.1152/ajpcell.00117.2009--Aquaporin 12 (AQPI2) is the most recently identified member of the mammalian AQP family and is specifically expressed in pancreatic acinar cells. In vitro expression studies have revealed that AQP12 is localized at intracellular sites. To determine the physiological roles of AQP12 in the pancreas, we generated knockout mice for this gene (AQP12-KO). No obvious differences were observed under normal conditions between wild-type (WT) and AQP12-KO mice in terms of growth, blood chemistry, pancreatic fluid content, or histology. However, when we induced pancreatitis through the administration of a cholecystokinin-8 (CCK-8) analog, the AQP12-KO mice showed more severe pathological damage to this organ than WT mice. Furthermore, when we analyzed exocytosis in the pancreatic acini using a two-photon excitation imaging method, the results revealed larger exocytotic vesicles (vacuoles) in the acini of AQP12-KO mice at a high CCK-8 dose (100 nM). From these results, we conclude that AQP12 may function in the mechanisms that control the proper secretion of pancreatic fluid following rapid and intense stimulation. pancreatic acinar cell: knockout mouse; pancreatic exocrine function; cholecystokinin; exocytosis doi: 10.1152/ajpcell.00117.2009

The renal cortical collecting duct (CCD) plays an important role in systemic acid-base homeostasis. The [beta]-intercalated cells secrete most of the HC[O.sup.-.sub.3], which is mediated by a luminal, DIDS-insensitive, [Cl.sup.-]/HC[O.sup.-.sub.3] exchange. The identity of the luminal exchanger is a matter of debate. Anion exchanger isoform 4 (AE4) cloned from the rabbit kidney was proposed to perform this function (Tsuganezawa H et al. J Biol Chem 276: 8180-8189, 2001). By contrast, it was proposed (Royaux IE et al. Proc Natl Acad Sci USA 98: 4221-4226, 2001) that pendrin accomplishes this function in the mouse CCD. In the present work, we cloned, localized, and characterized the function of the rat AE4. Northern blot and RT-PCR showed high levels of AE4 mRNA in the CCD. Expression in HEK-293 and LLC-P[K.sub.1] cells showed that AE4 is targeted to the plasma membrane. Measurement of intracellular pH (p[H.sub.i]) revealed that AE4 indeed functions as a [Cl.sup.-]/HC[O.sup.-.sub.3] exchanger. However, AE4 activity was inhibited by DIDS. Immunolocalization revealed species-specific expression of AE4. In the rat and mouse CCD and the mouse SMG duct AE4 was in the basolateral membrane. By contrast, in the rabbit, AE4 was in the luminal and lateral membranes. In both, the rat and rabbit CCD AE4 was in [alpha]-intercalated cells. Importantly, localization of AE4 was not affected by the systemic acid-base status of the rats. Therefore, we conclude that expression and possibly function of AE4 is species specific. In the rat and mouse AE4 functions as a [Cl.sup.-]/HC[O.sup.-.sub.3] exchanger in the basolateral membrane of [alpha]-intercalated cells and may participate in HC[O.sup.-.sub.3] absorption. In the rabbit AE4 may contribute to HC[O.sup.-.sub.3] secretion. anion exchanger isoform 4; 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid; submandibular gland; [alpha]-intercalated cells; kidney; cortical collecting duct

Stanniocalcin (STC) is a calcium- and phosphate-regulating hormone produced in bony fish by the corpuscles of Stannius, which are located close to the kidney. It is a major antihypercalcemic hormone in fish. As the corpuscles of Stannius are absent, and antihypercalcemic hormones are basically not necessary, in mammals, the discovery of a mammalian homolog, STC1, was surprising and intriguing. STC1 displays a relatively high amino acid sequence identity (~50%) with fish STC. In contrast to fish STC, STC1 is expressed in many tissues, including kidney. More recently, a human gene encoding the second stanniocalcin-like protein, STC2, was identified. STC2 has a lower identity (~35%) with STC1 and fish STC. Similar to STC1, STC2 is also expressed in a variety of tissues. Research into the functions of STCs in mammals is still at an early stage, and the ultimate physiological and pathological roles of STCs have not yet been established. A few studies indicate that STC1, similar to fish STC, stimulates phosphate absorption in the kidney and intestine, but the function of STC2 is still unknown. However, several interesting findings have been reported on their cellular localization, gene structure, and expression in different physiological and pathological conditions, which will be clues in elucidating the functions of STCs in mammals. STC1 expression is enhanced by hypertonicity in a kidney cell line or by ischemic injuries and neural differentiation in the brain. STC1 expression in the ovary is also enhanced during pregnancy and lactation. Calcitriol upregulates STC1 and downregulates STC2 expression in the kidney. Interestingly, STC1 and STC2 are expressed in many tumor cell lines, and the expression of STC2 is enhanced by estradiol in breast cancer cells. STC2 is also expressed in pancreatic islets. These results suggest that the biological repertoires of STCs in mammals will be considerably larger than in fish and may not be limited to mineral metabolism. This brief review describes recent progress in mammalian STC research. phosphate transport; calcium homeostasis; hypertonicity; ischemia

The CO1G6.1 is one of the eight cDNAs belonging to the major intrinsic protein superfamily found in the nematode Caenorhabditis elegans. The water channel function of the CO1G6.1 gene product is similar to that of aquaporin3 (AQP3) and glycerol facilitator (GlpF), but their osmotic water permeability and urea permeability are lower. Chimeric studies suggest that two segments of amino acid residues found in CO1G6.1, AQP3 and GlpF do not contribute to channel selectivity.

Research designed to establish the mercury inhibitory site in AQP3, an aquaporin (AQP) that has low homology to other AQPs, indicates that Cys-11 is the mercury-sensitive residue in AQP3. This residue could be independent of water channel function. Substitution of Cys-11 with tryptophan did not abolish water channel function. Mercury-sensitive cysteine may not be directly linked with the aqueous pore formation in AQP3. It is also possible that the side chain of Cys-11 may not extend into the pore.

The effects of dehydration on the distribution pattern and messenger ribonucleic acid (mRNA) expression of AQP3 were analyzed in rate kidney collecting ducts. Analysis of AQP3 mRNA expression in rat kidney collecting ducts indicated the role of dehydrationin inducing AQP3 expression at the protein level. Furthermore, analysis of AQP3 structure indicated that the water channel was a glycosylated protein with a structure that was similar to AQP1 and AQP2.

The presence of aquaporin (AQP) messenger ribonucleic acids (mRNAs) during kidney morphogenesis was analyzed by ribonuclease protection assay (RPA) and immunohistochemistry in fetal rats. Analyis of fetal rat kidneys by RPA and immunohistochemistry indicated the presence of AQP1, AQP3, AQP2 and AQP4 mRNA in the apical side of the cortical collecting duct cells. Furthermore, the imbalanced expression of AQP2 and AQP3/AQP4 in fetal rat kidneys indicated the presence of other water channel families in the basolateral membrane collecting ducts.

The administration of vasopressin in the apical membrane of collecting duct cells of Brattleboro rats results in an elevation of AQP-CD water channel. In the absence of vasopressin, the AQP-CD is spread in the cytoplasm but barely in the apical membrane of collecting duct cells. By introduction of vasopressin, the stored AQP-CD molecules are redistributed in the apical membrane.

Immunofluorescence- and immunoenzymatic histology reveal the localization of AQP-CD water channel in the apical side of the cell in kidney collecting ducts. Confocal fluorescence microcopic and electron microscopic studies reveal the localization of AQP-CD in the apical and endosomal membranes of the clear cells, but not of the mitochondria-rich, intercalated cells. Immunoblotting studies indicate AQP-CD as a 29-kDa protein and localization of this channel in the vasopressin-sensitive membranes of the kidney collecting duct principal cells support the membrane shuttle mechanism in the vasopressin diuresis mechanism.

Rabbit proximal convoluted tubules (PCT) were utilized in the identification of the transporters responsible for the chloride efflux across the basolateral cell membrane. Results suggest that the net chloride reabsorption is determined by the sodium-sensitive chloride-bicarbonate antiporter whilethe influence of the the other chloride transporters is negligible. Further, the basolateral chloride efflux is sufficient to account for the trancellular transport of chloride ions in the PCT.

Abstract Introduction Tumor-induced osteomalacia is a paraneoplastic syndrome of hypophosphatemia. Osteomalacia causes multiple bone fractures and severe pain. Case presentation We report the case of a 57-year-old Japanese man with tumor-induced osteomalacia associated with a middle cranial fossa bone tumor. The tumor was successfully resected by using a middle fossa epidural approach. His phosphate level recovered to a normal range immediately after the surgery. Conclusions It is rare that tumor-induced osteomalacia originates from the middle skull base. This report suggests that, if patients have a clinical and biochemical picture suggestive of tumor-induced osteomalacia, it is crucial to perform a meticulous examination to detect the tumor or the lesion responsible for the tumor. The serum level of fibroblast growth factor 23 is the most reliable marker for evaluating the treatment outcome of tumor-induced osteomalacia.