Gastric Mucosal Erosion in the Rat Following Administration of the Serotonin Precursor, 5-Hydroxytryptophan

Haverback, Bernard J.; Bogdanski, Donald F.

doi:10.3181/00379727-95-23232

Cited by 47 publications

(17 citation statements)

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“…However, the degree of acid back diffusion caused by aspirin in sympathectomized rats was found to be the same as that in sham operated animals. The pathogenesis of serotonin-induced ulcers has been reported (15,16), but such remains to be fully elucidated. Aures and Thompson (17) observed that serotonin contents were decreased in the stomach of immunosympathectomized rats.…”

Section: Discussionmentioning

confidence: 99%

Influence of Surgical Sympathectomy on Gastric Secretion and Ulceration in Rats

Kasuya

Murata

Okabe

1978

Japanese Journal of Pharmacology

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Abstract-The influences of sympathectomy on gastrointestinal mucosa, gastric secretion, acute or chronic gastric ulcers were studied in rats. Under ether anes thesia, sympathectomy was performed by surgical removal of the celiac ganglion. Surgical sympathectomy per se produced no pathological changes in the gastro intestinal tract as determined by macroscopical observation 3, 10 or 20 days after operation. The volume of gastric juice and pepsin output were not influenced by the sympathectomy but gastric acid output was significantly increased in pylorus-ligated rats. The sympathectomy worsened the stress-and the indomethacin-induced ulcer and delayed the healing of chronic gastric ulcers a little but not significantly, and had no deteriorative influence on the reserpine-induced ulcers. In contrast, Shay ulcers, aspirin-or serotonin-induced ulcers were significantly aggravated by sympathectomy. The loss of H+ ions and gain of Na+ ions in the gastric juice of pylorus-ligated and aspirin-treated rats were not affected by sympathectomy.Chemical or surgical sympathectomy has been performed by many workers in attempts to clarify the significance of sympathetic nervous system on gastric secretion or ulceration in man and experimental animals, but the data were controversial (1-6). Oberhelman et al.(3) observed the hypersecretion of gastric juice after surgical sympathectomy in dogs and suggested that deprivation of the sympathetic nerve supply to the stomach in ulcer patients worsens the condition. On the other hand, Rivilis (6) has reported that immunosympathec tomy failed to increase the acid secretion in pylorus-ligated rats, whereas acute gastric ulcers or hyperemia developed.Surgical sympathectomy was carried out in the present study to determine whether or not the sympathetic nervous system does have a significant influence on the integrity of gastric mucosa, secretion and the formation of various acute or chronic ulcers in rats. MATERIALS AND METHODSMale Donryu and Wistar strain rats were used.Synrpathectonry: Sympathectomy was performed according to the method established by one of the present authors (Y.K.) (7). Briefly, with the rat under ether anesthesia , the abdomen is incised and the celiac ganglion area exposed by dislocating the stomach, spleen and hepatic lobes. After careful elimination of fatty tissues around the ganglion, sympa thectomy is performed by removing the ganglion and cutting the postsynaptic nerve trunk along the celiac arteries. To ensure the denervation, the connective tissue between the stomach and spleen is also carefully resected. The completeness of sympathectomy is then confirmed by the disappearance of catecholamines from the stomach using fluorescence histochemical techniques. No fluorescence was observed 3 days after the operation. As the sham operation, the fatty tissue alone was resected and the celiac ganglion was simply confirmed.Examination of'pathological changes: Male Donryu rats, 200-250 g, were used. After sympathectomy or sham operation, the animals were maintained on ...

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Section: Discussionmentioning

confidence: 99%

Influence of Surgical Sympathectomy on Gastric Secretion and Ulceration in Rats

Kasuya

Murata

Okabe

1978

Japanese Journal of Pharmacology

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“…of the injection of large doses of 5-hydroxytryptophan. Reserpine in large doses had a similar effect (Benditt and Wong, 1957;Haverback and Bogdanski, 1957;Blackman, Campion, and Fastier, 1958). Some of the pharmacological actions of both these drugs appear to be mediated by 5-hydroxytryptamine.…”

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confidence: 86%

“…Other workers (Wilhelmi, 1957;Hedinger and Veraguth, 1957) have shown that 5-hydroxytryptamine in large doses causes gastric ulceration in the rat. The 5-hydroxytryptamine precursor, 5-hydroxytryptophan, has also been shown to produce gastric mucosal erosion in the rat (Haverback and Bogdanski, 1957). Haverback and Bogdanski (1957) observed that lesions after the administration of 5-hydroxytryptophan were fewer or even absent if the rats had been atropinized.…”

Section: Effect Of Iproniazidmentioning

confidence: 99%

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Mechanism of Action of Reserpine in Producing Gastric Haemorrhage and Erosion in the Mouse

Blackman

Campion

Fastier

1959

British Journal of Pharmacology and Chemotherapy

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Gastric haemorrhage was produced regularly in mice within 6 hours of the subcutaneous injection of a large dose (2 to 10 mg./kg.) of reserpine or of deserpidine. Rescinnamine,, and tetrabenazine (Ro 1-9569) were less active. Gastric haemorrhage was also produced within 6 hours when 5-hydroxytryptamine (10 mg./kg.) was injected every half-hour. Neither reserpine nor 5-hydroxytryptamine produced gastric haemorrbage in mice which had been vagotomized by tying the oesophagus at the cardio-oesophageal junction or which had been pre-treated with iproniazid. Amphetamine was less effective than iproniazid in preventing gastric haemorrhage after reserpine, and the following drugs were ineffective: cocaine, methyl phenidate (Ritalin), amarin, caffeine, nikethamide, lysergic acid diethylamide and its 2-bromo derivative (BOL148). Gastric haemorrhage was not observed in mice which had been given substantial doses of atropine or of hexamethonium before reserpine. The incidence of haemorrhage was substantially reduced by treatment with an antacid mixture. It is concluded that reserpine-like drugs cause gastric haemorrhage by a mechanism which has an important central component and which involves the liberation of 5-hydroxytryptamine.Haverback and have shown that gastric erosion was produced in rats within 18 hr. of the injection of large doses of 5-hydroxytryptophan. Reserpine in large doses had a similar effect (Benditt and Wong, 1957;Haverback and Bogdanski, 1957;Blackman, Campion, and Fastier, 1958). Some of the pharmacological actions of both these drugs appear to be mediated by 5-hydroxytryptamine. Reserpine liberates 5-hydroxytryptamine from platelets and certain other parts of the body, and interferes with the uptake of 5-hydroxytryptamine, while 5-hydroxytryptophan is the natural precursor to 5-hydroxytryptamine (Pletscher, Shore, and Brodie, 1955; Page, 1958). Therefore, when we observed in experiments on mice that large doses of reserpine produced gastric haemorrhage and melaena within a few hours (Blackman et al., 1958), we supposed at first that this was a peripheral effect brought about by an increase in " free " 5-hydroxytryptamine. The possibility that it was a central effect was raised by our observation that reserpine did not produce gastric haemorrhage in mice which had been vagotomized at the cardio-oesophageal junction. Another observation at variance with our original hypothesis was that reserpine did not produce gastric haemorrhage in mice which had been previously treated with iproniazid (Blackman et al., 1958). Since iproniazid is a powerful inhibitor of mono-amine oxidase and is believed to delay the destruction of 5-hydroxytryptamine in the body (Page, 1958), it would be expected to enhance rather than antagonize the harmful effect of reserpine on the gastric mucosa, were the erosion brought about by the local action of 5-hydroxytryptamine. These anomalous findings induced us to carry out the experiments reported here. METHODS Male mice weighing 30 to 40 g. were used. During the 24 hr. period precedi...

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“…Haverback and Bogdanski (10) reported that serotonin administered to rats in a dose of 300 mg/kg produced haemorrhagic mucosal erosions in the glandular por tion of the stomach and formation of these lesions was prevented by pretreatment with atropine sulfate. Blackman et al (11) also reported that serotonin as well as reserpine caused gastric haemorrhages in normal mice but not in the vagotomized mice and they concluded that reserpine-like drugs caused gastric haemorrhage by a mechanism which involved the liberation of central monoamines.…”

Section: Effects Of Dibenamine and Atropine A) Dibenaminementioning

confidence: 99%

Studies on the Experimental Gastrointestinal Ulcers Produced by Reserpine and Stress 3. Effects of Monoamines and Their Precursors

Doteuchi

1968

Japanese Journal of Pharmacology

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Kido (1) has shown that even a small dose of reserpine could produce severe ulcers in the gastrointestinal tract of cats when combined with stress, such as hypothalamic stim ulation and electrical shock through the grid on the floor of the cage. Hartry (2) and Sawrey and Sawrey (3) also reported that ulcers were produced by a small dose of reserpine and stress in rats.The author (4,5) previously reported that ulcer formation by reserpine and stress had a close correlation with the decrease in monoamines, i.e. serotonin and norepinephrine, in the gastrointestinal tract, and that syrosingopine and tetrabenazine could produce simi lar ulcers when combined with grid shock. From these findings he speculated that the decrease in peripheral as well as central monoamines contributed important factors in ulcer formation by reserpine and grid shock. If it is true that the decrease in monoamines is the cause of ulcer formation by reserpine and grid shock, it has to be inhibited by a re plenishment of monoamines or their precursors.In the present study, the effects of MAO inhibitor, monoamines and their precursors on ulcer formation by reserpine and grid shock were investigated. Moreover, the effects of drugs which block the autonomic nerves were also investigated to confirm the observa tion of Kido (1) that in splanchnectomized and vagotomized cats ulcers were hardly pro duced by reserpine and grid shock. METHODSOne hundred and twenty-two cats of both sexes weighing from 2.5 to 4.0 kg were used. All animals were deprived of food for 16 hours prior to the experiments. Reserpine was administered subcutaneously. Two hours later, cats were placed in individual cages equipped with grids on the floor and 5-seconds of electrical shock were given every 30 seconds for 4 hours to their body surfaces through the grids (abbreviated as grid shock). The intensity of grid shock was adjusted so that shocks always elicited invariable emotional responses.At the end of grid shocks, cats were sacrificed by decapitation under pentobarbital anesthesia. The stomach adjoining 15 cm of duodenum was removed, cut along the greater curvature and photographed. Thereafter the tissue was fixed in 10% of formalin

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Gastric Mucosal Erosion in the Rat Following Administration of the Serotonin Precursor, 5-Hydroxytryptophan

Abstract: Plrariiracolog~, S n t i o r i d Heart Zitst it r ( t t 3 , S . I .W ., Bet hasda, Maryland.

Cited by 47 publications

References 4 publications

Influence of Surgical Sympathectomy on Gastric Secretion and Ulceration in Rats

Influence of Surgical Sympathectomy on Gastric Secretion and Ulceration in Rats

Mechanism of Action of Reserpine in Producing Gastric Haemorrhage and Erosion in the Mouse

Studies on the Experimental Gastrointestinal Ulcers Produced by Reserpine and Stress 3. Effects of Monoamines and Their Precursors

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