Prostaglandins VIII: A proposed role for PGE2 in the genesis of stress-induced gastric ulcers

Usardi, M.M.; Franceschini, J; Mandelli, V.; Daturi, S.; Mizzotti, B.

doi:10.1016/0090-6980(74)90035-5

Cited by 22 publications

(5 citation statements)

References 14 publications

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“…Gastric ulceration induced by pyloric ligation in the rat has been shown to be inhibited by the subcutaneous infusion of prostaglandin E1 (Robert et al, 1968), prostaglandin E2 and prostaglandin F2 (Usardi et al, 1974). Gastric ulceration in the rat induced by indomethacin (Lippmann, 1974a) and by stress due to pyloric ligation (Carter et al, 1974, Lippmann, 1974c was inhibited by oral administration of synthetic prostaglandin analogues.…”

Section: Discussionmentioning

confidence: 99%

Effect of prostaglandin 15(R) 15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal haemorrhage in rats.

Carmichael¹,

Nelson²,

Russell³

et al. 1976

Gut

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SUMMARY The eflect of orally administered prostaglandin 15(R)15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal haemorrhage has been studied in rats. The incidence of haemorrhage induced by aspirin (26-7 mM), 64 mg/kg, together with taurocholic acid (2.5 mM), was significantly reduced from 53l6% to 19l5% by the addition of the prostaglandin (9-9 ,uM), P < 0 01. The incidence of haemorrhage induced by aspirin alone (53-3 mM), 128 mg/kg, was significantly reduced from 80% to 20% by the addition of prostaglandin (9-9 ,tM), P < 0-002.These results indicate the possible use of synthetic prostaglandins in the prevention of aspirininduced gastric pathology.It has long been known that aspirin ingestion in man produces gastric irritation which, on occasion, may progress to severe gastric erosions with haemorrhage. Semple and Russell (1975) have shown that the incidence of gastric mucosal bleeding induced by aspirin in rats is significantly increased by the addition of conjugated bile acids, especially taurocholic acid.Aspirin, in addition to other anti-inflammatory agents, has been shown to inhibit the synthesis of prostaglandins in vitro (Ferreira et al., 1971;Smith and Willis, 1971;Vane, 1971). Naturally occurring prostaglandins, especially El, E2, and A1, when given systemically, markedly inhibit gastric acid secretion in animals (Robert et al., 1967;Wilson and Levine, 1969) and in man (Classen et al., 1970;Wilson et al., 1971). Prostaglandin El has also been shown to inhibit the production of gastric ulceration in rats induced by stress after pyloric ligation (Robert et al., 1968). However, naturally occurring prostaglandins are rapidly degraded in the stomach when given orally and are largely ineffective by this route. In recent years, resistant synthetic analogues have been produced and can therefore be given orally with effect. Various workers have shown that certain of these analogues have an even greater 'Address for correspondence: Dr R. 1. Russell, Royal Infirmary, Glasgow, G4 OSF. Received for publication 20 October 1975 inhibitory effect on gastric secretion than the naturally occurring prostaglandins; this has been demonstrated in animals (Robert and Magerlein, 1973) and in man (Carter et al., 1973;Lippmann, 1974b). A more marked inhibitory effect has also been shown on gastric ulcer formation in the rat induced by indomethacin (Lippmann, 1974a) and by stress due to pyloric ligation (Carter et al., 1974).We have studied the effects of the synthetic analogue prostaglandin 15(R)15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal bleeding in rats.

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Section: Discussionmentioning

confidence: 99%

Effect of prostaglandin 15(R) 15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal haemorrhage in rats.

Carmichael¹,

Nelson²,

Russell³

et al. 1976

Gut

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“…PGE2 and K11550 injected s.c. immediately before stress (Usardi, Franceschini, Mandelli, Daturi & Mizzotti, 1974) to rats (130 + 10 g) fasted for 16 h but given free access to water, gave ED50 of 150 jig/kg (140 to 161) and 20.7 pg/kg (19.9 to 21.5) for protection from gastric lesions. Orally administered PGE2 and K11550 protected gastric mucosa at ED50 of 484 jg/kg (444 to 527) and 182 pg/kg (167 to 198).…”

Section: Controlsmentioning

confidence: 99%

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

1981

British J Pharmacology

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Some CCK-like peptides were tested for their effects on gastric emptying in the rat, taking into account their spasmogenic action on the gastroduodenal junction observed in previous papers (Bertaccini, Impicciatore & De Caro, 1973; Bertaccini, Impicciatore, De Caro, Chiavarini & Burani, 1974). Gastric emptying of a phenol red meal was evaluated by a modification (Scarpignato and Bertaccini, 1980) of the method described by Reynell & Spray (1956). Male rats weighing 200 g were used after a fasting period of 24 h. Peptides used were: caerulein, C-terminal heptapeptide of CCK (hepta-CCK) and pentagastrin. They were injected i.p. in a constant volume of 1 ml/kg 5 min prior to administration of the meal. Rats were killed at various time intervals to evaluate the duration of the effect. A fixed time (20 min) was selected for the study of the dose-response relationship. All the peptides delayed gastric emptying in a dosedependent fashion: threshold doses were 0.075 .g/kg for caerulein and hepta-CCK. Both peptides caused a complete block of gastric emptying with doses of 5 gg/kg. Pentagastrin had a threshold dose at 10 pg/kg; the maximum dose (80 pg/kg) caused an 104P PROCEEDINGS OF THE B.P.S., 30th JUNE, 1st JULY, 1980 Table I 'Characteristics' of emptying patterns Calculated Half-life emptying time Treatment (min) (min) Controls 15.3 + 6.2' 120.9 + 6.1 Caerulein (1 bg/kg) 49.0 + 14.32 220.6 + 14.32 Hepta-CCK (1 p.g/kg) 53.3 + 14.32 289.3 + 14.22 Pentagastrin (80 bg/kg) 23.8 + 7.73 146.0 + 7.73 1 Mean value + 95W confidence limits. 2 Statistically significant difference (P < 0.001) in comparison with control values. Statistically significant difference (P < 0.01) in comparison with control values. suggest that the delay in gastric emptying induced by CCK-like peptides is connected with the contraction of the pylorus pointed out in previous studies. Therefore the pyloric sphincter appears to play an important role in the regulation of emptying of liquids in rats, unlike cats and dogs (Stemper & Cooke, 1976) in which gastric emptying of liquids was shown to be independent of the gastroduodenal junction.

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“…In such preparations, whilst the partial agonist may not itself produce a response, the stimulus generated by the partial agonist still contributes to the overall effect of agonist/partial agonist combinations according to the equation: In our first paper (Andreani et al,1983) we reported the synthesis and antitumour activity of two compounds (2,3)related to the local anaesthetic ketocaine. The subsequent papers (Andreani et al,1984,Andreani et al,1983 concerned the analogues 4 -13 while a new series ( 14-21) was published later (Andreani et al, 1984" ).…”

Section: Treatmentmentioning

confidence: 99%

“…In this study we It has been reported that methyl esters(ME)of certain amino acids such as L-Leucine lead to lysosomal disfunction and cardiac toxicity (1), while other ME such as L-Arginine ME (LAM) exhibit a strong protective activity against ultrastructural and functional damage induced on the isolated perfused guinea pig in ischemic and reperfusion conditions (2). In order to verify in a vivo model the function of LAM, the antiarrhythmic activity (AA) of amino acid arginine (LA) and two of its ME, LAM and benzoil arginine ME (BAM) was assessed against arrhythmias occurring during 30 min.…”

Section: Pmentioning

confidence: 99%

“…Thus, after treatment with 90, 150 or 300 mg/kg of barbitone followed by THC (20 mg/kg), the proportion of mice losing their RR was respectively 0, 66.7 and 100%. 2,5, has been shown to deplete nigrostriatal dopamine of the mouse when given by repeated systemic injection (Heikkila et al, 1984;Bradbury et al, 1985). (1984) Nature 311, 467-469 Bradbury, A.J.…”

Section: Pmentioning

confidence: 99%

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Poster Communications

1985

British J Pharmacology

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It is well known that the anticonvulsant effect of antiepileptic drugs is reduced by repeated administration in both experimental animals and man (Frey and Kampmann, 1965; Masuda et al., 1979; Rawling et al., 1975). The purpose of this investigation was to verify if denzimol, an arylalkylimidazole anticonvulsant agent (Nardi et al., 1981; Graziani et al., 1983) induces tolerance after repeated treatment in mice. Phenobarbitone (PB) and carbamazepine (CB) were used as reference drugs.We have investigated the antielectroshock activity (MES) and the brain levels of denzimol, after acute and repeated treatment, to verify whether the development of denzimol tolerance involves mechanisms of adaptation of the central nervous system or an induction of hepatic microsomial enzymes.Three groups of 20 mice each were treated p.o. for 14 days with denzimol (30 mg/kg), PB (25 mg/kg) or CB (30 mg/kg). Three control groups of mice received the vehicle (0.5% methocel). 24 hours after the end of the prolonged treatment, the respective drugs and vehicle, at the same dose as above, were given to the treated and control groups of animals. The anticonvulsant effect of each drug against MES was examined at 1,2,4,6,8 hrs after the last administration. The protection against the tonic extension of forelimb (TFP) and hindlimb (THP) induced by MES was the criterium used for the assessment of positive response.After MES, animals treated with denzimol were sacrificed and brains were removed for tissue drug levels evaluation (Abbiati et al. 1985).The present study shows that repeated administrations of PB, CB and denzimol resulted in a development of tolerance to their anticonvulsant action. Tolerance induced by denzimol against TFP and THP extension, resulted lower than that of PB and probably of CB. When denzimol was administered in a single dose to denzimol tolerant mice, its brain concentrations was markedly reduced if compared to non-tolerant mice. Moreover the disappearance of brain denzimol concentrations, after a single dose of drug, was alterated by repeated treatment of mice with denzimol. These findings seem to suggest that decreased anticonvulsant activity of denzimol, following repeated administrations, might be due to a development of pharmacokinetic tolerance.Abbiati G.A., Restelli G.V., Graziani G., Testa R. (1985) In previous experim-ents we have shown that prolactin (PRL) secretion in avian species is under a tonic inhibitory control of dopa;-iine (disticb et al.,1979). The present study was carried out in order to assess the role played b, cholinergic mechanisms in the control of PRL secretion in pigeons (Columba livia). In particular, we have assessed the effects of drugs enhancing by different mechanisms cholinergic transmiission, i.e. carbachol, muscarine and physostigmine, on morphology (studied by SEM5 and TEll) of crop-sac mlucosa and pituitary lactoWrophs.Carbachol, microinfused into the III cerebral ventricle (6 nrmiol) for 3 consecutive days, produced intense crop-sac stimulation with rmiilk-like secretion and...

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Prostaglandins VIII: A proposed role for PGE2 in the genesis of stress-induced gastric ulcers

Cited by 22 publications

References 14 publications

Effect of prostaglandin 15(R) 15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal haemorrhage in rats.

Effect of prostaglandin 15(R) 15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal haemorrhage in rats.

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

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