Electron microscopic identification of the histamine-storing argyrophil (enterochromaffin-like) cells in the rat stomach

Håkanson, R.; Owman, Ch.; Sporrong, B.; Sundler, F.

doi:10.1007/bf00936080

Cited by 98 publications

(36 citation statements)

References 11 publications

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“…Nuclei contained prominent nucleoli and wellstained chromatin, but were otherwise unremarkable. These findings are consistent with those described for ECL cells in rats (20,22,26) and in man Although there were no carcinoid tumors at 55 mg/kg of BL-6341 or in the rats receiving the reference compound (cimetidine at 950 mglkg), proliferations of argyrophil endocrine cells could be detected in these groups at both 1 and 2 years by use of appropriate silver stains. At 1 year, the argyrophil endocrine cell increase was significantly greater than in controls at both 300 and 55 mg/kg of BL-6341 (Table 11).…”

Section: Two-year Ratsupporting

confidence: 90%

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Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H₂-Receptor Antagonist, BL-6341

et al. 1988

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Oral administration of BL-634 1 hydrochloride, a long-acting histamine H2-receptor antagonist, to rats for 2 years at doses of 10, 55 or 300 rng/kdday resulted in several changes in the fundic (oxyntic) mucosa of the glandular stomach. The most significant alteration was a proliferation of argyrophil endocrine cells that was demonstrated to be enterochromaffin-like (ECL) cells. The ECL cell proliferation consisted of a continuum of changes involving diffuse hyperplasia, focal adenomatous hyperplasia, and carcinoid tumor formation at the highest dose level of 300 mg/kg. At 55 mg/kg only ECL celI hyperpIasia occurred, and at the low dose of 10 mg/kg there were no remarkable proliferative changes. The reference compound, cimetidine (950 mg/ kg), produced a degree of ECL cell proliferation that was slightly less, but not significantly different than, that observed with 55 mg/kg of BL-6341. Dose-related elevations of serum gastrin were observed with BL-634 1 , while cimetidine produced hypergastrinemia that was generally intermediate between that produced by the middle and low doses of BL-634 1. The hypergastrinemia resulted from the pharmacologic inhibition of acid secretion, which is the negative feedback mechanism controlling the production of gastrin. Only the 300 rng/kg dose of BL-6341 produced a significant, sustained (24 hours) hypergastrinemia and carcinoid tumors. The chronic, sustained hypergastrinemia was considered to be the primary cause of the ECL cell carcinoid neoplasia. All genetic toxicology tests performed with BL-634 1 were negative. It was concluded that the demonstrated hypergastrinemia represents an indirect, hormonal, epigenetic mechanism of tumorigenesis. INTRODU~IONThe toxicologic testing of new, potent, long-acting histamine H,-receptor antagonists and H+, K+-ATPase inhibitors has resulted in several types of proliferative gastric changes in chronic rat studies. The most noteworthy of these is the occurrence of gastric carcinoid tumors in the oxyntic mucosa (2, 18, 34). These proliferative endocrine changes are distinct from those produced by the gastric carcinogen, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), that produces adenocarcinomas primarily in the pylonc region of the stomach (28). The histamine H,-blocker, tiotidine, has produced a dysplasiakarcinoma syndrome in rats that resembles the lesions associated with MNNG (38).This report describes the occurrence of proliferative, gastric, endocrine cell changes in the fundic stomach of rats administered the long-acting H,-antagonist, BL-6341 hydrochloride. It discusses the significance of these lesions, proposes a mechanism of tumorigenesis, and compares these observations with similar findings associated with other anti-secretagogues and those reported in man. METHODS Two-Year RatStudy. The carcinogenicity study was composed of 60 male and 60 female Charles R.iver, Sprague-pawley CD rats per dose group, and 110 male and 110 female negative controls. Rats were 8 weeks of age when the study was initiated.. They were administered ei...

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Section: Two-year Ratsupporting

confidence: 90%

“…The results of these silver stains, especially the Sevier-Munger technique, suggested that the carcinoid tumors were composed of enterochromaffinlike (ECL) cells (20,22,23). The immunoperoxidase technique demonstrated the presence of histamine in the proliferated endocrine cells in the fundic mucosa.…”

Section: Two-year Ratmentioning

confidence: 99%

Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H₂-Receptor Antagonist, BL-6341

et al. 1988

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“…They comprise ive major cell populations: gastrin cells and 5-hydroxytryptamine-storing enterochromaffin cells in the pyloric gland area (Hakanson, 1970; Larsson, HAkanson, Rehfeld, Stadil & Sundler, 1974); somatostatin cells which have a fairly uniform distribution in the entire glandular mucosa (cf. Alumets, Sundler & HAkanson, 1977); and histamine-storing 'enterochromaffin-lilie' cells which are of two different types, ECL and A-like cells, both of which occur in the oxyntic gland area where they are very numerous (HAkanson & Owman, 1967, 1969 HAkanson, Owman, Sporrong & Sundler, 1971; see also Solcia, Capella, Vassallo & Buffa, 1975).…”

Section: Introductionmentioning

confidence: 99%

Effect of antrum exclusion on endocrine cells of rat stomach.

Alumets¹,

Munshid²,

Håkanson³

et al. 1979

The Journal of Physiology

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SUMMARY1. Following antrum exclusion the serum gastrin concentration was raised and independent of the prandial state. The antral gastrin concentration and number of gastrin cells were greatly lowered.2. The histamine content and the number of histamine-storing endocrine ('enterochromaffin-like') cells in the oxyntic mucosa was almost doubled and the mucosal histidine decarboxylase activity was greatly elevated following antrum exclusion. 3. At the ultrastructural level both types of histamine-storing endocrine cells (ECL and A-like) were found to be enlarged and to have a reduced number of granules per unit cytoplasm. These changes are compatible with an increased secretory activity. The G (gastrin) cells were not increased in size but their granule volume density was lowered.4. We propose that antrum exclusion results in uninhibited gastrin release causing profound changes in the histamine-storing endocrine cells of the oxyntic mucosa. The cells respond to the hypergastrinemia by an increase in functional activity (activation of histidine decarboxylase and reduction of granule volume density) as well as by an increase in number and size.

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“…Further physiological studies are required to elucidate the ways in which the distribution of gastrointestinal endocrine cells may be related to regulatory characteristics of the digest tract. Gastrointestinal endocrine cells not only have endocrine function, but also have the exocrine and paracrine effect (Bülbring & Crema, 1959;Håkanson, et al, 1971;Uvnäs-Wallensten & Rehfeld, 1976). In this paper, the argentaffine cells could be observed in the intrinsic membrane, or their protrusions extended into the intrinsic membrane and a lot of secretory granules was obvious around the protrusions, these morphologic basis proved that the sections of argentaffine cells can get though the intrinsic membrane and then into the blood circulation to exercise its function, thus confirmed the endocrine function of argentaffine cells.…”

Section: Discussionmentioning

confidence: 99%

Argentaffine Cells in the Digestive Tract of Hibernating and Non-hibernating in Chinese Fire-bellied Newt (Cynops orientalis)

Xie

Guo

et al. 2012

Int. J. Morphol.

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SUMMARY:In order to further studying the relationship between the gastrointestinal endocrine cells and the hibernation of Chinese fire-bellied newt, histological techniques were used in this study to explore the distributed density and morphology of argentaffine cells in the digestive tract during hibernation and non-hibernation. The argentaffine cells could be observed throughout the digestive tract of Chinese fire-bellied newt during hibernation and non-hibernation and mainly distributed in the acinar epithelial cells, epithelial cells and intrinsic membrane. They had appeared in the shape of goblet, pyramid, ellipse, round, cone-shaped, spindle-shaped. The cytoplasm contains secretory granules at the basal regions with spherical nuclei in the basal regions. Most of them had processes in different directions, suggesting that the argentaffine cells have combined the function of endocrine and exocrine. The distribution density curves of argentaffine cells were generally wavelike during the two periods. It was highest in the body of stomach in hibernation, while in nonhibernation it was highest in the pyloric. Totally the density of argentaffine cells was higher in hibernation period than that in nonhibernation period. The results showed that the activity of the digestive tract was expectedly weakened during the hibernation, but the function of endocrine was actually strengthened.

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Electron microscopic identification of the histamine-storing argyrophil (enterochromaffin-like) cells in the rat stomach

Cited by 98 publications

References 11 publications

Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H₂-Receptor Antagonist, BL-6341

Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H₂-Receptor Antagonist, BL-6341

Effect of antrum exclusion on endocrine cells of rat stomach.

Argentaffine Cells in the Digestive Tract of Hibernating and Non-hibernating in Chinese Fire-bellied Newt (Cynops orientalis)

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Electron microscopic identification of the histamine-storing argyrophil (enterochromaffin-like) cells in the rat stomach

Cited by 98 publications

References 11 publications

Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H2-Receptor Antagonist, BL-6341

Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H2-Receptor Antagonist, BL-6341

Effect of antrum exclusion on endocrine cells of rat stomach.

Argentaffine Cells in the Digestive Tract of Hibernating and Non-hibernating in Chinese Fire-bellied Newt (Cynops orientalis)

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Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H₂-Receptor Antagonist, BL-6341

Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H₂-Receptor Antagonist, BL-6341