PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9696704

Electrogenic bicarbonate secretion in mouse gallbladder.

L C Martin·M E Hickman·C M Curtis·L J MacVinish·A W Cuthbert
View original source ↗Export metadata ↓

Abstract

Mouse gallbladders (4 mm2) were investigated using the short-circuit current (Isc) technique. Responses of 50 microA/cm2 were obtained in response to forskolin and agents that stimulated the adenylate cyclase system (IBMX and dibutyryl-cAMP). The calcium ionophore ionomycin increased Isc to 30% of the forskolin-stimulated increase. The forskolin-dependent current was inhibited 40% by acetazolamide but was insensitive to furosemide. Forskolin responses were dependent on the presence of bicarbonate ions; removal from both sides of the membrane or the basolateral side alone caused a significant reduction in responses. Removal of chloride ions from the basolateral side had no effect, while removal from the apical side caused a significant reduction in the forskolin responses, but only by 30%. It is argued that the remaining current (70%) cannot result from a parallel arrangement of a chloride channel and a chloride-bicarbonate exchanger and that bicarbonate is secreted through the apical membrane by a predominantly conductive mechanism. Apparently, forskolin converts a near electrically silent epithelium to an electrogenically secreting tissue.

Explore related subjects

1-Methyl-3-isobutylxanthineAdenylyl CyclasesAnimalsBicarbonatesBucladesineChloridesColforsinElectric ConductivityEpitheliumGallbladderIonomycinIonophoresMembrane PotentialsMiceJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

L C Martin, M E Hickman, C M Curtis, L J MacVinish, A W Cuthbert. 1998. Electrogenic bicarbonate secretion in mouse gallbladder.. https://doi.org/10.1152/ajpgi.1998.274.6.g1045

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Hormonal induction of adipogenesis induces Skp2 expression through PI3K and MAPK pathways.

We have previously shown that the F-box protein, S-phase kinase-associated protein (Skp2) plays a mechanistic role in targeting the cell-cycle inhibitor, p27 for degradation by the 26S proteasome during early stages of 3T3-L1 adipocyte differentiation. Here, we demonstrate that protein levels of Skp2 and its accessory protein, Cks1 increased as density-arrested preadipocytes re-entered the cell cycle during clonal expansion, decreased with differentiation-induced growth arrest, and became refractory to hormonal stimulation following the onset of terminal adipocyte differentiation. Component analysis revealed that while maximal Skp2/Cks1 protein accumulation required the complete differentiation cocktail, that insulin was principally involved. Skp2 mRNA accumulation was found to precede the increase in Skp2 protein and succeed the activation of Akt and Erk1/2, mediators of phosphatidylinositol-3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) signal transduction pathways, respectively. Using specific inhibitors, we found that while activation of both pathways was required for maximal expression, PI3K signaling was primarily responsible for the increase in Skp2/Cks1 accumulation. The increase in Skp2 mRNA was notable 4 h following hormonal stimulation, plateaued by 12 h during mid-G1 phase progression, and occurred without change to mRNA stability. We further demonstrate that luciferase activity, originating from a pGL3 vector containing 2.4 kb of the Skp2 promoter, increased 2.5-fold with hormonal stimulation. This increase in promoter activity was markedly suppressed following PI3K and MAPK blockade. Deletion studies indicate that responsive elements were located within the proximal Skp2 promoter. These data demonstrate that Skp2 is transcriptionally regulated by PI3K and MAPK pathways as 3T3-L1 preadipocytes transition from quiescence to proliferation during adipocyte hyperplasia.

1-Methyl-3-isobutylxanthine↗
PubMed2007

Meiotic competence and acetylation pattern of UV light classified mouse antral oocytes after meiotic arrest with isobutylmethylxanthine.

Chromatin transformation from a diffused or NSN configuration to a compacted or SN shape that forms a ring around the nucleolus is regarded as one of the modifications necessary for successful embryonic development. But the process of the transformation is poorly understood. In this study we cultured mouse antral oocytes under meiotic arrest with IBMX for periods between 3 and 24 hr. We observed the chromatin status of the oocytes before and after culture under UV illumination. We reported here that the NSN configured oocytes transformed temporally through an intermediate form into the SN configuration while under meiotic arrest in vitro. Meiotic rate was improved in the NSN oocytes after the meiotic arrest but decreased in the SN oocytes. We also reported that chromatin of both the NSN and SN oocytes was acetylated and the two groups underwent the same pattern of H4/K5 deacetylation during meiotic maturation. We hypothesized that the transformation of mouse oocyte from the NSN to SN type may be time rather than oocyte size specific and the abrupt deacetylation of NSN oocyte during spontaneous maturation may explain its poor meiotic and developmental competence.

1-Methyl-3-isobutylxanthine↗
PubMed2006

TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi.

Cyclic nucleotide phosphodiesterases (PDEs) catalyze the degradation of cAMP and cGMP, and regulate a variety of cellular processes by controlling the levels of these second messengers. We have previously described the presence of both a calcium-stimulated adenylyl cyclase and two membrane-bound cAMP-specific PDEs (one of them strongly associated to the flagellum and the other one with a possible vesicular localization) in Trypanosoma cruzi. Here we report the identification and characterization of TcrPDEA1, a singular phosphodiesterase of T. cruzi which is resistant to the typical phosphodiesterase inhibitors, such as IBMX, papaverine and theofylline. TcrPDEA1 is a single copy gene that encodes a 620-amino acid protein, which is grouped with PDE1 family members, mainly with its kinetoplastid orthologs. TcrPDEA1 was able to complement a mutant yeast strain deficient in PDE genes, demonstrating that this enzyme is a functional phosphodiesterase. TcrPDEA1 is specific for cAMP with a high K(m) value (191.1+/-6.5 microM). Cyclic GMP neither activates the enzyme nor competes as a substrate. In addition, calcium-calmodulin did not affect the kinetic parameters and, as its counterpart in T. brucei, magnesium showed to be crucial for its activity and stability. Although TcrPDEA1 function remains unclear, its presence points out the high complexity of the cAMP signaling in trypanosomatids and the possible compartmentalization of the enzymes involved in the cAMP pathway.

1-Methyl-3-isobutylxanthine↗