Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetazolamide (Ace) is a putative inhibitor of carbonic anhydrase (CA), an enzyme that catalyzes the equilibration of carbon dioxide and carbonic acid and plays a key role in HCO(3)(-) and water reabsorption and acid secretion. Aquaporins (AQPs) are channel-forming membrane glycoproteins that mediate water reabsorption by the renal tubules and other organs of mammals. AQP1 and CAII or CAIV share many common biological properties. Previous studies have shown that AQP1 and CA are located at the same sites in cells of the male reproductive tract. In the present study, Ace at a dose of 40 mg/kg/d x 14, administered per os, suppressed AQP1 gene expression and inhibited CA activity in rat testis. On day 7 of treatment the epididymal sperm motility was significantly reduced, while on day 14 a decrease in sperm count occurred. Ace caused a marked downregulation of AQP1 gene expression; significant suppression occurred on days 7 and 14. Moreover, CA activity was totally blocked throughout the treatment period. The present findings suggest that the reduction of rat sperm motility and count by Ace can be attributed to its capacity to downregulate AQP1 water channel gene expression.
 ...
PMID:Influence of acetazolamide on AQP1 gene expression in testis and on sperm count/motility in epididymis of rats. 1213 89

Water content within the epididymis of the male reproductive system is stringently regulated to promote sperm maturation. Several members of the aquaporin (AQP) family of water channel-forming integral membrane proteins have been identified in epididymal cells, but expression profiling for this epithelium is presently incomplete, and no AQP isoform has yet been identified on basolateral plasma membranes of these cells. In this study, we explored AQP expression by RT-PCR and light microscopy immunolocalizations using peroxidase and wide-field fluorescence techniques. The results indicate that several AQPs are coexpressed in the epididymis including AQP 5, 7, 9, and 11. Immunolocalizations suggested complex patterns in the spatial distribution of these AQPs. In principal cells, AQP 9 and 11 were present mainly on microvilli, whereas AQP 7 was localized primarily to lateral and then to basal plasma membranes in a region-specific manner. AQP 5 was also expressed regionally but was associated with membranes of endosomes. Additionally, AQPs were expressed by some but not all basal (AQP 7 and 11), clear (AQP 7 and 9), and halo (AQP 7 and 11) cells. These findings indicate unique associations of AQPs with specific membrane domains in a cell type- and region-specific manner within the epididymis of adult animals.
 ...
PMID:Membrane domain specificity in the spatial distribution of aquaporins 5, 7, 9, and 11 in efferent ducts and epididymis of rats. 1879 8

Murine epididymal spermatozoa were dispersed in a medium of native osmolality and then transferred to a hypo-osmotic medium to mimic the physiological osmotic challenge, as encountered upon ejaculation into the female tract. The addition of quinine to block sperm K(+)-channels for volume regulation resulted in a size increase of viable cells. Preincubation in 0.1 mM HgCl(2), a standard aquaporin inhibitor, prevented such cell swelling. Addition of the K(+)-ionophore valinomycin to quinine-swollen sperm reversed the swelling, but not after pretreatment of the swollen sperm by HgCl(2). Aqp7, Aqp8, and Aqp9 mRNAs were identified in spermatozoa by RT-PCR, and the entire open reading frames were sequenced and compared with the GenBank database. Western blotting demonstrated specific protein signals for sperm AQP7 and AQP8 expression but probably not AQP9. The role of Hg(2+)-insensitive AQP7, if any, in sperm volume regulation was studied in transgenic mice. Spermatozoa from Aqp7(-/-) mice were the same size as wild-type sperm in basal conditions. Quinine-swollen volume, swelling reversal by valinomycin, and inhibition by Hg(2+) were also similar, indicating efficient water transport in the absence of AQP7. However, both water influx and efflux occurred faster in Aqp7(-/-) sperm than wild-type. This faster water movement in the knockout mouse spermatozoa was explainable by an upregulation of Aqp8 expression as revealed by quantitative PCR. Therefore, the Hg(2+)-sensitive AQP8, which was localized in elongated spermatids and spermatozoa, is a likely candidate for a water channel responsible for physiological sperm volume regulation crucial to in vivo fertilization.
 ...
PMID:Aquaporin isoforms involved in physiological volume regulation of murine spermatozoa. 1882 4

Water and solute transport in the efferent ducts and epididymis are important for the establishment of the appropriate luminal environment for sperm maturation and storage. Aquaporin 9 (AQP9) is the main water channel in the epididymis, but its regulation is still poorly understood. Components of the kinin-kallikrein system (KKS), leading to the production of bradykinin (BK), are highly expressed in the lumen of the male reproductive tract. We report here that the epididymal luminal fluid contains a significant amount of BK (2 nM). RT-PCR performed on epididymal epithelial cells isolated by laser capture microdissection (LCM) showed abundant BK type 2 receptor (Bdkrb2) mRNA expression but no type 1 receptor (Bdkrb1). Double-immunofluorescence staining for BDKRB2 and the anion exchanger AE2 (a marker of efferent duct ciliated cells) or the V-ATPase E subunit, official symbol ATP6V1E1 (a marker of epididymal clear cells), showed that BDKRB2 is expressed in the apical pole of nonciliated cells (efferent ducts) and principal cells (epididymis). Triple labeling for BDKRB2, AQP9, and ATP6V1E1 showed that BDKRB2 and AQP9 colocalize in the apical stereocilia of principal cells in the cauda epididymidis. While uniform Bdkrb2 mRNA expression was detected in the efferent ducts and along the epididymal tubule, marked variations were detected at the protein level. BDKRB2 was highest in the efferent ducts and cauda epididymidis, intermediate in the distal initial segment, moderate in the corpus, and undetectable in the proximal initial segment and the caput. Functional assays on tubules isolated from the distal initial segments showed that BK significantly increased AQP9-dependent glycerol apical membrane permeability. This effect was inhibited by BAPTA-AM, demonstrating the participation of calcium in this process. This study, therefore, identifies BK as an important regulator of AQP9.
 ...
PMID:Segmental expression of the bradykinin type 2 receptor in rat efferent ducts and epididymis and its role in the regulation of aquaporin 9. 1882 5

The aquaporin-7 (AQP7) water channel is known to be a member of the aquaglyceroporins, which allow the rapid transport of glycerol and water. In this chapter, we review the physiological functions of AQP7 in the kidney and the male reproductive system.In the kidney, AQP7 is abundantly present at the apical membrane of the proximal straight tubules. Although the contribution of AQP7 to the water permeability of proximal straight tubules was found to be minimal compared with that of AQP1, we identified a novel glycerol reabsorption pathway that may be important for preventing glycerol from being excreted into urine.In the male reproductive system, AQP7 is present particularly in the spermatids, as well as in the testicular and epididymal spermatozoa, suggesting that AQP7 has some role in late spermatogenesis. However, male AQP7 knockout mice were not sterile, and their sperm did not show any morphological or functional abnormalities.
 ...
PMID:Function of aquaporin-7 in the kidney and the male reproductive system. 1909 80

Maintaining tight control over body fluid and acid-base homeostasis is essential for human health and is a major function of the kidney. The collecting duct is a mosaic of two cell populations that are highly specialized to perform these two distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor, the V2R, play a central role in regulating the urinary concentrating mechanism by stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical membrane of collecting duct principal cells. This increases epithelial water permeability and allows osmotic water reabsorption to occur. An understanding of the basic cell biology/physiology of AQP2 regulation and trafficking has informed the development of new potential treatments for diseases such as nephrogenic diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule acidification due to the activation of intercalated cells is also critical to organ function, and defects lead to several pathological conditions in humans. Therefore, it is important to understand how these "professional" proton-secreting cells respond to environmental and cellular cues. Using epididymal proton-secreting cells as a model system, we identified the soluble adenylate cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal intercalated cells also express sAC and respond to cAMP by increasing proton secretion, supporting the hypothesis that sAC could function as a luminal sensor in renal tubules to regulate acid-base balance. This review summarizes recent advances in our understanding of these fundamental processes.
 ...
PMID:New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells. 2246 Jul 10