Aspirin potentiates prestimulated acid secretion and mobilizes intracellular calcium in rabbit parietal cells.

Levine, Robert A.; Nandi, Jyotirmoy; King, Rebecca

doi:10.1172/jci114725

Cited by 27 publications

(26 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…respect to possible alternative mechanisms of airway epithelial HCO 3 Ϫ secretion, we failed to detect evidence of an anion exchanger that might be regulated by CFTR on the apical membrane of airway epithelium (22) (26). Taken together, these data indicate that CF cultures lack the capacity to secrete HCO 3 Ϫ to match H ϩ ,K ϩ -ATPase-mediated proton secretion into ASL under basal and cAMP-stimulated conditions, resulting in ''hyperacidification'' of ASL.…”

Section: Discussionmentioning

confidence: 70%

Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium

Coakley

Grubb

Paradiso

et al. 2003

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

269

302

View full text Add to dashboard Cite

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR)-dependent airway epithelial bicarbonate transport is hypothesized to participate in airway surface liquid pH regulation and contribute to lung defense. We measured pH and ionic composition in apical surface liquid (ASL) on polarized normal (NL) and CF primary bronchial epithelial cell cultures under basal conditions, after cAMP stimulation, and after challenge with luminal acid loads. Under basal conditions, CF epithelia acidified ASL more rapidly than NL epithelia. Two ASL pH regulatory paths that contributed to basal pH were identified in the apical membrane of airway epithelia, and their activities were measured. We detected a ouabain-sensitive (nongastric) H ؉ ,K ؉ -ATPase that acidified ASL, but its activity was not different in NL and CF cultures. We also detected the following evidence for a CFTR-dependent HCO 3 ؊ secretory pathway that was defective in CF: (i) ASL [HCO 3 ؊ ] was higher in NL than CF ASL; (ii) activating CFTR with forskolin͞3-isobutyl-1-methylxanthine alkalinized NL ASL but acidified CF ASL; and (iii) NL airway epithelia more rapidly and effectively alkalinized ASL in response to a luminal acid challenge than CF epithelia. We conclude that cultured human CF bronchial epithelial pH ASL is abnormally regulated under basal conditions because of absent CFTRdependent HCO 3 ؊ secretion and that this defect can lead to an impaired capacity to respond to airway conditions associated with acidification of ASL.

show abstract

Section: Discussionmentioning

confidence: 70%

Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium

Coakley

Grubb

Paradiso

et al. 2003

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

269

302

View full text Add to dashboard Cite

show abstract

“…For example, trafficking of aquaporin-2 to the apical membrane of collecting duct principal cells in response to vasopressin is dependent on intracellular calcium release from ryanodine-sensitive stores (7). Intracellular calcium also regulates H ϩ -K ϩ -ATPase in both the stomach and the colon (20,26,28,39), 10% CO 2 -dependent stimulation of CCD H ϩ -K ϩ -ATPase (52), and collecting duct H ϩ -ATPase stimulation by metabolic acidosis (38,43). Finally, intracellular calcium plays a role in SNARE-protein-mediated vesicle fusion with plasma membranes (27).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms through which ammonia regulates cortical collecting duct net proton secretion

Frank

Wingo

Andrews

et al. 2002

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Ammonia stimulates cortical collecting duct (CCD) net bicarbonate reabsorption by activating an apical H+-K+-ATPase through mechanisms that are independent of ammonia's known effects on intracellular pH and active sodium transport. The present studies examined whether this stimulation occurs through soluble N-ethylmaleimide-sensitive fusion attachment receptor (SNARE) protein-mediated vesicle fusion. Rabbit CCD segments were studied using in vitro microperfusion, and transepithelial bicarbonate transport was measured using microcalorimetry. Ammonia's stimulation of bicarbonate reabsorption was blocked by either chelating intracellular calcium with 1,2-bis(2-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid acetoxymethyl ester or by inhibiting microtubule polymerization with colchicine compared with parallel studies performed in the absence of these inhibitors. An inactive structural analog of colchicine, lumicolchicine, did not alter ammonia's stimulation of bicarbonate reabsorption. Tetanus toxin, a zinc endopeptidase specific for vesicle-associated SNARE (v-SNARE) proteins, prevented ammonia from stimulating net bicarbonate reabsorption. Consistent with the functional evidence for v-SNARE involvement, antibodies directed against a conserved region of isoforms 1–3 of the tetanus toxin-sensitive, vesicle-associated membrane protein (VAMP) members of v-SNARE proteins labeled the apical and subapical region of collecting duct intercalated cells. Similarly, antibodies to NSF protein, a protein involved in activation of SNARE proteins for subsequent vesicle fusion, localized to the apical and subapical region of collecting duct intercalated cells. These results indicate that ammonia stimulates CCD bicarbonate reabsorption through an intracellular calcium-dependent, microtubule-dependent, and v-SNARE-dependent mechanism that appears to involve insertion of cytoplasmic vesicles into the apical plasma membrane of CCD intercalated cells.

show abstract

“…Different in vivo studies carried out in humans have demonstrated that both acetylsalicylic acid and indomethacin are able to increase the basal rate of acid formation (8,12,21,29) and to potentiate acid secretion stimulated by histamine (21,29). Furthermore, in vitro studies carried out in isolated rabbit fundic glands (48), in preparations of rat gastric mucosa (41), or in isolated rabbit parietal cells (27,28,37) have demonstrated that micromolar concentrations of aspirin and other NSAIDs, like indomethacin, piroxicam, and naproxen, may potentiate gastric acid secretion stimulated by histamine, dibutyryl cAMP, or forskolin without affecting the basal rate of acid formation. The biochemical mechanism of this potentiation is not well established.…”

mentioning

confidence: 99%

Inhibition of acid secretion by the nonsteroidal anti-inflammatory drugs diclofenac and piroxicam in isolated gastric glands: analysis of a multifocal mechanism

Salvatella¹,

Rossi²,

Valle³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

In nonstimulated rabbit gastric glands, acetylsalicylic acid (10-500 microM) and indomethacin (3-300 microM) did not significantly modify the basal rate of acid secretion, whereas diclofenac and piroxicam (10-1,000 microM each) caused a marked and dose-dependent inhibitory effect (EC(50) = 138 and 280 microM, respectively). In gastric glands stimulated by histamine (100 microM), diclofenac also reduced the rate of acid formation in a dose-dependent manner. In contrast, acetylsalicylic acid, indomethacin, and piroxicam exerted a biphasic effect; thus low concentrations (3-100 microM) of these three agents significantly increased the rate of histamine-stimulated acid secretion (10-20% over the corresponding control value) by a cAMP-independent mechanism, whereas higher concentrations reduced the rate of acid formation. With respect to underlying biochemical mechanisms that could mediate inhibitory effects of NSAIDs on gastric acid formation, it was observed that both diclofenac and piroxicam, but not acetylsalicylic acid or indomethacin, decreased the glandular content of ATP, inhibited hydrolytic activity of gastric gland microsomal H(+)-K(+)-ATPase, and reduced the rate of H(+)-K(+)-ATPase-dependent proton transport across microsomal membranes in a dose-dependent manner. Furthermore, diclofenac and piroxicam also significantly increased passive permeability of microsomal membranes to protons. In conclusion, our work shows that diclofenac and piroxicam cause a significant reduction in the rate of basal and histamine-stimulated acid formation in isolated rabbit gastric glands at concentrations that can be attained in the gastric lumen of patients treated with these drugs. Mechanisms involved in these inhibitory effects appear to be multifocal and include different steps of stimulus-secretion coupling.

show abstract

Aspirin potentiates prestimulated acid secretion and mobilizes intracellular calcium in rabbit parietal cells.

Cited by 27 publications

References 44 publications

Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium

Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium

Mechanisms through which ammonia regulates cortical collecting duct net proton secretion

Inhibition of acid secretion by the nonsteroidal anti-inflammatory drugs diclofenac and piroxicam in isolated gastric glands: analysis of a multifocal mechanism

Contact Info

Product

Resources

About