Summary
In the rat, gastric histamine is stored predominantly in the enterochromaffin-like (ECL) cells, which are located basally in the oxyntic mucosa. The functional significance of histamine in the ECL cells is a matter of speculation. In this study the effect of depletion of histamine on the properties and ultrastructure of the ECL cells was examined. Histamine synthesis was inhibited with α-fluoromethylhistidine (3 mg·kg-1·h-1) given via osmotic minipumps over a period of 24 h. The treatment reduced the histidine decarboxylase activity (approximately 20% remaining) and histamine concentration (less than 20% remaining) in the oxyntic mucosa, as well as the intensity of histamine- and chromogranin A-immunostaining in the ECL cells, compared to control rats. The cytoplasmic (secretory) granules/vesicles were greatly reduced in number and size following α-fluoromethylhistidine administration. The histamine immunostaining of the mast cells, which occurs at the mucosal surface and in the submucosa, appeared unaffected. We conclude that ECL cell histamine accounts for at least 80% of the total oxyntic mucosal histamine in the rat and that it represents a more mobile pool than mast cell histamine. The reduction in the number and size of the ECL cell granules/vesicles following histamine depletion is in accord with the idea that they represent the storage site for histamine.
Similar content being viewed by others
References
Alumets J, El Munshid HA, Håkanson R, Liedberg G, Oscarsson J, Rehfeld JF, Sundler F (1979) Effect of antrum exclusion on endocrine cells of rat stomach. J Physiol (Lond) 286:145–155
Alumets J, ElMunshid HA, Håkanson R, Hedenbro J, Liedberg G, Oscarson J, Rehfeld JF, Sundler F, Vallgren S (1980) Gastrin cell proliferation after chronic stimulation: Effect of vagal denervation or gastric surgery in the rat. J Physiol (Lond) 298:558–569
Andersson K, Mattsson H, Larsson H (1990) The role of gastric mucosal histamine in acid secretion and experimentally induced lesions in the rat. Digestion 46:1–9
Andersson K, Håkanson R, Mattsson H, Ryberg B, Sundler F (1992) Hypergastrinemia induces hyperplasia of histamine-depleted ECL cells in the rat stomach. Gastroenterology (in press)
Børglum Jensen T, Fahrenkrug J, Sundler F (1991) Immunocytochemical localisation of pancreastatin and chromogranin A in porcine neuroendocrine tissues. Regul Pept 36:283–297
Bouclier M, Jung MJ, Gerhart F (1983a) α-Fluoromethylhistidine. Inhibition of histidine decarboxylase in pylorus ligated rats. Biochem Pharmacol 32:1553–1556
Bouclier M, Jung MJ, Gerhart F (1983b) Effect of prolonged inhibition of histine decarboxylase on tissue histamine concentrations. Experientia 39:1303–1305
Böttcher G, Håkanson R, Nilsson G, Seensalu R, Sundler F (1989) Effects of long-term hypergastrinaemia on the ultrastructure of enterochromaffin-like cells in the stomach of the rat, hamster and guinea pig. Cell Tissue Res 256:247–257
Cetin Y, Grube D (1991) Immunoreactivities for chromogranin A and B and secretogranin II in the guinea pig entero-endocrine systems. Cellular distributions and intracellular heterogeneities. Cell Tissue Res 264:231–241
Curry WJ, Johnston CF, Shaw C, Buchanan KD (1990) Distribution and partial characterisation of immunoreactivity to the putative C-terminus of rat pancreastatin. Regul Pept 30:207–219
Delwaide J, Belaiche J, Courtoy R, Vivario M, Louis E, Gast P, Boniver J (1991) Ultrastructural demonstration of histamine in human enterochromaffin like cell granules. Gut 32:834
Duggan DE, Hooke KF, Maycock AL (1984) Inhibition of histamine synthesis in vitro and in vivo by s-α-fluoromethylhistidine. Biochem Pharmacol 33:4003–4009
Enerbäck L (1966) Mast cells in rat gastrointestinal mucosa. II. Dye-binding and metachromatic properties. Acta Pathol Microbiol Scand 66:303–312
Håkanson R, Liedberg G (1970) The role of endogenous gastrin activation of gastric histidine decarboxylase in the rat. Effect of antrectomy and vagal denervation. Eur J Pharmacol 12:94–103
Håkanson R, Liedberg G (1972) Effects of brocresine (NSD-1055) and cycloheximide on amino acid decarboxylase activities in gastric mucosa of normal and vagally denervated rats. Br J Pharmacol 46:688–695
Håkanson R, Kroensen JH, Liedberg G, Oscarson J, Rehfeld JF, Stadil F (1974) Correlation between serum gastrin concentration and rat stomach histidine decarboxylase activity in the rat. J Physiol (Lond) 243:483–498
Håkanson R, Alumets J, Rehfeld JF, Ekelund M, Sundler F (1982) The life cycle of the gastrin granule. Cell Tissue Res 222:479–491
Håkanson R, Böttcher G, Ekblad E, Panula P, Simonsoson M, Dohlsten M, Hallberg T, Sundler F (1986a) Histamine in endocrine cells in the stomach: A survey of several species using a panel of histamine antibodies. Histochemistry 86:5–17
Håkanson R, Oscarson J, Sundler F (1986b) Gastrin and the trophic control of gastric mucosa. Scand J Gastroenterol [Suppl] 118:18–30
Håkanson R, Persson P, Axelson J (1990a) Elevated serum gastrin after food intake or acid blockade evokes hypocalcemia. Regul Pept 28:131–136
Håkanson R, Persson P, Axelson J, Johnell O, Sundler F (1990b) Evidence that gastrin enhances 45Ca uptake into bone through release of a gastric hormone. Regul Pept 28:107–118
Kahlson G, Rosengren E, Svensson SE (1973) Histamine and gastric acid secretion with special reference to the rat. In: Holton P (ed) The Pharmacology of Gastrointestinal Motility and Secretion, section 39A, vol 1. International encyclopaedia of pharmacology and therapeutics. Pergamon Press, Oxford, pp 41–102
Koyama S, Oishi R, Saeki K (1987) Effects of pentagastrin and carbachol on gastric histamine levle in α-fluoromethylhistidine-treated mice and rats. Naunyn-Schmiedebergs Arch Pharmacol 336:387–390
Kubota H, Taguchi T, Tohyama M, Matsuura N, Shiosaka S, Ishihara T, Watanabe T, Shiotani Y, Wada H (1984) Electron microscopic identification of histidine decarboxylase-containing endocrine cells of the rat gastric mucosa: an immunohistochemical analysis. Gastroentereology 87:496–502
Larsson H, Carlsson E, Mattsson H, Lundell L, Sundler F, Sundell G, Wallmark B, Watanabe T, Håkanson R (1986) Plasma gastrin and gastric enterochromaffin-like cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats. Gastroenterology 90:391–399
Lönroth H, Håkanson R, Lundell L, Sundler F (1990) Histamine-containing endocrine cells in the human stomach. Gut 31:383–388
Maeyama K, Watanabe T, Taguchi Y, Yamatodani A, Wada H (1982) Effect of α-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, on histamine levels in mouse tissues. Biochem Pharmacol 31:2367–2387
Pearse AGE, Polak JM (1975) Bifunctional reagents as vapour-and liquid-phase fixatives for immunohistochemistry. Histochem J 7:179–186
Persson P, Håkanson R, Axelson J, Sundler F (1989) Gastrin releases a blood calcium-lowering peptide from the acid-producing part of the rat stomach. Proc Natl Acad Sci USA 86:2834–2838
Ryberg B, Mattsson H, Larsson H, Carlsson E (1989) Correlation between inhibition of gastric acid secretion, plasma gastrin and oxyntic mucosal histidine decarboxylase activity in the rat. Scand J Gastroenterol 24:287–292
Ryberg B, Axelson J, Håkanson R, Sundler F, Mattsson H (1990) Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat. Gastroenterology 98:33–38
Sandvik AK, Lewin MJM, Waldum HL (1989) Histamine release in the totally isolated vasculary perfused rat stomach — regulation by autoreceptor. Br J Pharmacol 96:557–562
Simonsson M, Eriksson S, Håkanson R, Lind T, Lönroth H, Lundell L, O'Connor DT, Sundler F (1988) Endocrine cells in the human oxyntic mucosa. A histochemical study. Scand J Gastroenterol 23:1089–1099
Sjövall M, Ekblad E, Lundell L, Sundler F (1990) Gastrin-releasing peptide: Neuronal distribution and spatial relation to endocrine cells in the human upper gut. Regul Pept 28:47–55
Snyder SH, Epps L (1968) Regulation of histidine decarboxylase in rat stomach by gastrin: the effect of inhibitors of protein synthesis. Mol Pharmacol 4:187–195
Weibel ER (1969) Stereological principles for morphometry in electron microscopic cytology. Int Rev Cytol 26:235–302
Weibel ER, Bolender RP (1973) Stereological techniques for electron microscopic morphometry. In: Hayat MA (ed) Principles and techniques of electron microscopy. Biological applications, vol. 3. Van Nostrand Reinhold, New York, pp 237–296
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Andersson, K., Chen, D., Håkanson, R. et al. Enterochromaffin-like cells in the rat stomach: effect of α-fluoromethylhistidine-evoked histamine depletion. Cell Tissue Res. 270, 7–13 (1992). https://doi.org/10.1007/BF00381874
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00381874