Nonsalicylate nonsteroidal antiinflammatory drugs augment prestimulated acid secretion in rabbit parietal cells

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

doi:10.1016/0016-5085(91)90536-t

Cited by 17 publications

(14 citation statements)

References 32 publications

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“…Furthermore, these findings were highly consistent with the lack of statistically significant changes in the glandular content of ATP, in the hydrolytic activity of microsomal H ϩ -K ϩ -ATPase, and in the rate of the H ϩ -K ϩ -ATPase-dependent proton transport across microsomal membranes observed in response to all the assayed concentrations of either acetylsalicylic acid or indomethacin. Moreover, our data are in good agreement with those previously reported by Levine et al (27,28) that showed that neither acetylsalicylic acid nor indomethacin significantly modified the hydrolytic activity of H ϩ -K ϩ -ATPase assayed in rabbit gastric microsomes.…”

Section: Discussionsupporting

confidence: 96%

“…On the one hand, acetylsalicylic acid (10-1,000 M) and indomethacin (3-300 M) did not significantly modify the rate of [ 14 C]aminopyrine uptake in gastric glands incubated under basal conditions. These results confirm previous reports that showed that neither of these two NSAIDs affected the basal rate of acid formation in 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). Furthermore, these findings were highly consistent with the lack of statistically significant changes in the glandular content of ATP, in the hydrolytic activity of microsomal H ϩ -K ϩ -ATPase, and in the rate of the H ϩ -K ϩ -ATPase-dependent proton transport across microsomal membranes observed in response to all the assayed concentrations of either acetylsalicylic acid or indomethacin.…”

Section: Discussionsupporting

confidence: 94%

“…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.…”

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confidence: 97%

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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

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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.

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Section: Discussionsupporting

confidence: 96%

Section: Discussionsupporting

confidence: 94%

mentioning

confidence: 97%

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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

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“…Aspirin and other non-salicylate NSAIDs have been reported to increase or potentiate histamine stimulated acid secretion in vivo5 6 and in vitro in different animal models, [7][8][9][10][11] suggesting that enhanced gastric acid secretion could play a part in the pathogenesis of NSAID induced gastroduodenal mucosal damage. The mechanisms of NSAID stimulated acid secretion have been extensively explored by Levine et al [7][8][9] in an in vitro rabbit parietal cell model, suggesting that NSAID induced acid secretion is regulated by the presence of calcium and the inhibition of prostaglandins.…”

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confidence: 99%

Non-steroidal anti-inflammatory drugs and prostaglandin effects on pepsinogen secretion by dispersed human peptic cells.

Lanas

Nerín

Esteva

et al. 1995

Gut

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The effects of aspirin and ibuprofen on pepsinogen secretion were studied in isolated human peptic cells prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and percoli gradient centrifugation. Pharmacological concentrations of aspirin and ibuprofen (10-8-10-4 M), potentiated histamine (10-6-10-4 M) and forskolin (10-5 M) inhibition and seems to act on pepsinogen Dr A I Lanas, Servicio de secretion at a post-receptor site.Aparato Digestivo, Hospital. Gul9365763Clinico Universitario, 50009 (Gut 1995; 36: 657-663) Zaragoza, Spain.

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“…It was reasoned that enhanced gastric acid secretion may be involved in the pathogenesis of NSAID-induced gastric damage. For example, Levine et al [61] published that indomethacin, naproxen and carprofen potentiated the histamine-, forskolin-, dibutyryl cAMP-stimulated acid secretion in isolated rabbit parietal cells. Similarly, aspirin was found to induce morphological transformation of the secretory state in isolated rabbit parietal cells [62].…”

Section: Injurious Factors and Nsaidsmentioning

confidence: 97%

Some of the factors that may mediate or modify the gastrointestinal mucosal damage induced by non-steroidal anti-inflammatory drugs

Gyires

1994

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Numerous factors are involved in the gastrointestinal mucosal damage induced by non-steroidal anti-inflammatory drugs. The physico-chemical-acidic-property of the drugs is responsible partly for the rapid absorption, mucosal accumulation and barrier breaking effect, partly for the topical irritant action. The drugs decrease the defensive mechanisms of the stomach at different level, destroy the mucosal barrier, decrease the surface hydrophobicity, the mucosal blood flow, and inhibit the prostaglandin synthesis. Exogenous sulfhydryls and interleukin-1 inhibit the NSAID-induced mucosal damage, whether they are also involved in the ulcerogenic action has not been clearly determined. On the other hand, injurious factors are also stimulated; enhanced gastric acid secretion, increased pepsin activity, enhanced formation of free radicals and leukotrienes, as well as activation of leukocyte can also contribute to the mucosal lesions induced by NSAIDs. Prior Campylobacter pylori infection may make the mucosa more susceptible to NSAID-associated injury.

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Nonsalicylate nonsteroidal antiinflammatory drugs augment prestimulated acid secretion in rabbit parietal cells

Cited by 17 publications

References 32 publications

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

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

Non-steroidal anti-inflammatory drugs and prostaglandin effects on pepsinogen secretion by dispersed human peptic cells.

Some of the factors that may mediate or modify the gastrointestinal mucosal damage induced by non-steroidal anti-inflammatory drugs

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