Biomedical subjects

F Sundler

Publications and source records attributed to F Sundler.

At least 19 recordsLinked to original sources

PubMed1992

Helospectin-like immunoreactivity in the esophagus.

Helospectin I and II are two non-amidated, VIP-like peptides, isolated from the salivary gland venom of the lizard Heloderma horridum. The lower esophagus of cat, sheep and man was analyzed for helospectin-like immunoreactivity. Immunocytochemistry revealed helospectin-immunoreactive nerve fibers in the muscle layers, submucosa and mucosa of all species studied. In myenteric ganglia helospectin-immunoreactive nerve fibers and nerve cell bodies could be seen. Double immunostaining for helospectin and vasoactive intestinal peptide (VIP) revealed their coexistence in nerve fibers and cell bodies throughout the lower esophagus of all species tested. Double immunostaining for helospectin and neuropeptide Y revealed their coexistence in nerve fibres surrounding vascular and non-vascular smooth muscle. In the cat and sheep (but not in man) a subpopulation of the helospectin/VIP-containing fibers stored, in addition, substance P. The helospectin-immunoreactive material in the esophagus probably constitutes a novel neuropeptide. The distribution of the VIP/helospectin-immunoreactive neurons and fibers indicates their possible involvement in the regulation of motor and secretory activities.

Animals↗

PubMed1992

Neonatal capsaicin-treatment in mice: effects on pancreatic peptidergic nerves and 2-deoxy-D-glucose-induced insulin and glucagon secretion.

It is not known whether sensory nerves are involved in the insulin, glucagon or glucose responses to autonomic nerve activation induced by 2-deoxy-D-glucose (2-DG). We therefore treated mice neonatally with capsaicin which permanently destroys sensory afferent nerve fibers. Immunohistochemistry of the pancreas at 13-14 weeks of age revealed a substantial reduction of calcitonin gene-related peptide (CGRP)-immunoreactive nerves and a partial reduction of substance P-immunoreactive nerves. In contrast, no effect was observed on galanin-immunoreactive nerves. At age 10-12 weeks, the mice were injected intravenously with 2-DG (500 mg/kg). In controls, 2-DG stimulated insulin and glucagon secretion and induced hyperglycemia (P less than 0.01). Capsaicin treatment partially reduced the glucose and glucagon responses to 2-DG (P less than 0.01). In contrast, the insulin response to 2-DG was not affected by capsaicin. It is concluded that the mouse pancreas contains capsaicin-sensitive sensory CGRP- and substance P-immunoreactive nerve fibers, whereas the galanin-immunoreactive nerve fibers are not sensitive to capsaicin. Furthermore, capsaicin-sensitive sensory nerve fibers are partially involved in 2-DG-induced glucagon secretion and hyperglycemia, whereas sensory nerves are not involved in 2-DG-induced insulin secretion.

Animals↗

PubMed1992

Distribution and co-localization of immunoreactive helospectin with vasoactive intestinal polypeptide and peptide histidine methionine in human nasal mucosa, soft palate and larynx.

Regulatory peptide immunoreactivities reported in the upper respiratory system of man include vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), which are co-localized in a network of fine varicose nerve fibers. The present study was undertaken to examine the possible occurrence and distribution of the recently described VIP-like peptide helospectin. Double immunofluorescence labelling showed that helospectin is co-localized with VIP and PHM. In addition to nerve fibers containing all three peptides, scattered nerve fibers were detected that were only immunoreactive to helospectin but not to VIP and/or PHM. The distribution of helospectin/VIP/PHM immunoreactive nerve fibers around blood vessels and in close relationship to seromucous glands indicates their possible involvement in the regulation of blood flow and secretion.

Fluorescent Antibody Technique↗

PubMed1992

Pituitary adenylate cyclase-activating polypeptide (PACAP): occurrence in rodent pancreas and effects on insulin and glucagon secretion in the mouse.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that occurs in several tissues, e.g., in the gut. We have studied PACAP-like immunoreactivity in the pancreas of rat and mouse, and the effects of PACAP-38 on basal and stimulated insulin and glucagon secretion in the mouse. Immunofluorescence staining demonstrated the presence of PACAP-like immunoreactivity in nerve fibers in both the rat and mouse pancreas. The nerve fibers were seen in the exocrine pancreas and surrounding the islets. Occasionally, the nerve fibers occurred within the islets. Most PACAP-positive nerve fibers innervated the intrapancreatic ganglia, although no nerve cell bodies contained PACAP-like immunoreactivity. In-vivo experiments in mice revealed that basal plasma glucagon levels were increased by PACAP-38 injected intravenously at dose levels exceeding 1.8 nmol/kg. Furthermore, PACAP-38 (7 nmol/kg) potentiated the plasma glucagon response to the cholinergic agonist carbachol (0.16 mumol/kg). This potentiation was reduced to simple addition by pretreatment with a combined alpha- and beta-adrenergic blockade by phentolamine (35 mumol/kg) and propranolol (8.5 mumol/kg). Moreover, PACAP-38 inhibited a carbachol-induced increase in the level of plasma insulin in the absence but not in the presence of adrenergic blockade. PACAP-38 increased basal plasma insulin levels and increased basal plasma glucose levels 6 min and 10 min, respectively, after injection of the peptide. We conclude that PACAP-like immunoreactivity exists in nerve fibers innervating the mouse and rat pancreas, particularly the intrapancreatic ganglia, and that PACAP-38 augments both basal and carbachol-stimulated glucagon secretion in the mouse.

Animals↗

PubMed1992

Localization of calcitonin gene-related peptide and islet amyloid polypeptide in the rat and mouse pancreas.

It was previously demonstrated that the two chemically related peptides calcitonin gene-related peptide (CGRP) and islet amyloid polypeptide (IAPP) both occur in the pancreas. We have now examined the cellular localization of CGRP and IAPP in the rat and the mouse pancreas. We found, in both the rat and the mouse pancreas, CGRP-immunoreactive nerve fibers throughout the parenchyma, including the islets, with particular association with blood vessels. CGRP-immunoreactive nerve fibers were regularly seen within the islets. In contrast, no IAPP-immunoreactive nerve fibers were demonstrated in this location. Furthermore, in rat islets, CGRP immunoreactivity was demonstrated in peripherally located cells, constituting a major subpopulation of the somatostatin cells. Such cells were lacking in the mouse islets. IAPP-like immunoreactivity was demonstrated in rat and mouse islet insulin cells, and, in the rat, also in a few non-insulin cells in the islet periphery. These cells seemed to be identical with somatostatin/CGRP-immunoreactive elements. In summary, the study shows (1) that CGRP, but not IAPP, is a pancreatic neuropeptide both in the mouse and the rat; (2) that a subpopulation of rat somatostatin cells contain CGRP; (3) that mouse islet endocrine cells do not contain CGRP; (4) that insulin cells in both the rat and the mouse contain IAPP; and (5) that in the rat, a non-insulin cell population apparently composed of somatostatin cells stores immunoreactive IAPP. We conclude that CGRP is a pancreatic neuropeptide and IAPP is an islet endocrine peptide in both the rat and the mouse, whereas CGRP is an islet endocrine peptide in the rat.

Amyloid↗

PubMed1992

A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: evidence for reduced content in Hirschsprung's disease.

A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), exhibits sequence homology with vasoactive intestinal polypeptide (VIP) and occurs in the mammalian brain, lung and gut. The distribution of PACAP in ganglionic and aganglionic portions of the large intestine of patients with Hirschsprung's disease was examined by immunohistochemistry and radioimmunoassay. PACAP-immunoreactive nerve fibers were distributed in all layers of the ganglionic and aganglionic segments of the intestine, although they were less numerous in the latter, and PACAP-immunoreactive nerve cell bodies were seen in the ganglionic portion of the intestine. The concentration of immunoreactive PACAP was lower in the aganglionic than in the ganglionic segment of the intestinal wall. PACAP and VIP were found to coexist in both ganglionic and aganglionic segments of the intestine. Apparently, PACAP participates in the regulation of gut motility. The scarcer PACAP innervation of the aganglionic segment may contribute to the defect in intestinal relaxation seen in patients with Hirschsprung's disease.

Ganglia↗

PubMed1992

Enterochromaffin-like cells in the rat stomach: effect of alpha-fluoromethylhistidine-evoked histamine depletion. A chemical, histochemical and electron-microscopic study.

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 alpha-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 alpha-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.

Animals↗

PubMed1992

Immunohistochemical characterization of endocrine cells in experimental exocrine pancreatic cancer in the Syrian golden hamster.

Fifty exocrine pancreatic adenocarcinomas and 57 benign tumors induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) were examined for the presence of argyrophil cells antiinsulin, -glucagon, -somatostatin, -pancreatic polypeptide (PP), -gastrin/CCK, -vasoactive intestinal polypeptide (VIP), and - neuron-specific enolase (NSE) reactive cells. Argyrophil - and antihormone-reactive cells were found in the normal pancreatic ducts and in the acini, as well as in hyperplastic and atypical ducts/ductules, tubular complexes, benign lesions, and in 80% of ductal adenocarcinomas. Insulin and antiNSE-reactive cells were the most common, followed in decreasing frequency by glucagon, somatostatin, and PP cells. Antigastrin-/CCK-and -VIP-reactive cells were found in two cases. Argyrophil cells were present in about 60% of the tumors with Grimelius staining and in 55% of those with Churukian-Schenk staining. Insulin cells were seen in ductal cancer that had grown into a lymph node and in the lymph node metastases of another cancer. A novel finding was the presence of argyrophil and insulin cells within the lumen of some malignant glandular structures. Coexistence of several peptide cells was found in 52% of the cancers. The presence of argyrophil and hormone-producing cells in induced pancreatic ductal/ductular lesions further strengthens the existence of a close developmental relationship between exocrine and endocrine cells of the pancreas.

Adenocarcinoma↗

PubMed1992

Hyperplasia of histamine-depleted enterochromaffinlike cells in rat stomach using omeprazole and alpha-fluoromethylhistidine.

In the rat, gastric histamine is stored mainly in the enterochromaffinlike cells. Gastrin releases histamine from these cells, and long-term hypergastrinemia results in hyperplasia. The effect of sustained hypergastrinemia on histamine-depleted enterochromaffinlike cells was studied by measuring histidine decarboxylase activity and histamine concentrations and by using quantitative histology. Hypergastrinemia maintained for 6 weeks was induced by inhibition of gastric acid secretion with omeprazole (400 mumol.kg-1.day-1) given orally, and histamine synthesis was inhibited for the same length of time with alpha-fluoromethylhistidine (3 mg.kg-1.h-1) given via osmotic minipumps. In rats given omeprazole alone, the effects of the resulting hypergastrinemia on the enterochromaffinlike cells was reflected in increased histidine decarboxylase activity, increased histamine concentration, and increased number of enterochromaffinlike cells. The general trophic effects on the stomach were seen as increased stomach and oxyntic mucosal weight and increased mucosal thickness. Treatment with alpha-fluoromethylhistidine plus omeprazole markedly reduced the histidine decarboxylase activity and histamine concentration, but the weight of the stomach and oxyntic mucosa, the enterochromaffinlike cell density, and intensity of histidine decarboxylase immunostaining were increased to at least the same extent as after omeprazole alone. These observations indicate that enterochromaffinlike cell histamine is not important for a full expression of gastrin-evoked trophic effects in the stomach.

Animals↗

PubMed1992

Helospectin-like peptides in the gastrointestinal tract: immunocytochemical localization and immunochemical characterization.

Helospectins I and II are two non-amidated, vasoactive intestinal peptide (VIP)-like peptides, isolated from the salivary gland venom of the lizard Heloderma horridum. Helospectin I has 38 amino acid residues and differs from helospectin II in that it has an additional serine residue at the C-terminus. The study was based on an antiserum that recognizes both helospectins I and II (but recognizes VIP only poorly). Immunocytochemistry of the digestive tract revealed helospectin-immunoreactive nerve fibers in the muscle layers, submucosa and mucosa of mouse, rat, hamster, guinea-pig and man. Myenteric and submucous ganglia in all species contained helospectin-immunoreactive nerve fibers and cell bodies. The distribution of helospectin-like immunoreactivity in the gut resembled that of VIP. Double immunostaining for helospectin and VIP revealed their co-existence in the same population of nerve fibers and cell bodies throughout the gut of all species tested. In addition, helospectin (but not VIP) immunoreactivity was observed in a population of endocrine cells in the intestines. The existence of helospectin-like material in the gut was confirmed by immunochemistry. The helospectin-like immunoreactivity in the extracts diluted in parallel to the helospectin standard curve. Analysis by high performance liquid chromatography of extracts of rat intestine revealed one predominant helospectin-immunoreactive peak that eluted close to authentic helospectins I and II. The helospectin-immunoreactive material in the gut may constitute a novel neuropeptide that co-exists with VIP. The distribution of the VIP-helospectin-immunoreactive neurons and fibers indicates their possible involvement in the regulation of gut motor and secretory activities.

Animals↗

PubMed1992

Pituitary adenylate cyclase activating peptide: a novel vasoactive intestinal peptide-like neuropeptide in the gut.

Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal peptide (VIP)-like hypothalamic peptide occurring in two forms, PACAP-27 and the C-terminally extended PACAP-38. The predicted rat and human PACAP sequence is identical to the isolated ovine one. In the present study, the occurrence and distribution of PACAP-like peptides were examined in the gut of several species by immunocytochemistry and immunochemistry using an antibody raised against PACAP-27. PACAP-like immunoreactivity was observed in nerve fibers in the gut wall of all species examined (chicken, mouse, rat, hamster, guinea-pig, ferret, cat, pig, sheep and man). In the chicken and human gut, immunoreactive fibers were numerous in all layers. In the other species examined the fibers were predominantly found in the myenteric ganglia and smooth muscle. Delicate PACAP-immunoreactive fibers were seen in the gastric mucosa of mouse, rat, hamster and man but not in the other species examined. The chicken proventriculus harbored numerous PACAP-immunoreactive endocrine cells which were identical with the serotonin-containing cells storing gastrin-releasing peptide. PACAP-immunoreactive nerve cell bodies were numerous in the submucous ganglia and moderate in number in the myenteric ganglia of the human gut. They were few in the intramural ganglia of the other species examined. Extrinsic denervation (performed on segments of rat and guinea-pig small intestine) did not visibly affect the PACAP innervation, indicating an intramural origin of most PACAP-immunoreactive fibers. Double immunostaining for VIP and PACAP revealed co-existence of the two peptides in nerve cell bodies and nerve fibers of the human and chicken gut and in fibers in the gastric mucosa of mouse and rat. In all other species examined and in all other locations in the gut PACAP-immunoreactive nerve cell bodies and nerve fibers were distinct from those storing VIP; many of them contained gastrin-releasing peptide instead. Immunochemistry revealed PACAP-like peptides in gut extracts of all species studied; upon high performance liquid chromatography the immunoreactive material co-eluted with synthetic PACAP-27. The distribution of PACAP-immunoreactive nerve cell bodies and nerve fibers in the gut wall suggests their involvement in the regulation of both motor and secretory activities.

Amino Acid Sequence↗

PubMed1992

Helodermin- and helospectin-like immunoreactivities in the rat brain: an immunochemical and immunohistochemical study.

Helodermin is an amidated peptide of 35 amino acid residues isolated from the lizard Heloderma suspectum. Homologous peptides, helospectins I and II, peptides of 38 and 37 amino acid residues, respectively, have been isolated from the lizard Heloderma horridum. This group of peptides stimulates the adenylate cyclase activity. Helodermin- and helospectin-like immunoreactivities were studied in the rat brain by using immunohistochemistry and radioimmunoassay in combination with high-performance liquid chromatography. The highest concentrations of helodermin-like immunoreactivity were found in the cerebellum and hypothalamus. The chromatographic analysis of rat brain extract revealed one main immunoreactive peak with elution properties similar to those of authentic lizard helodermin. Helodermin-immunoreactive neurons were located in the supraoptic nucleus, suprachiasmatic nucleus, periventricular nucleus, arcuate nucleus and central gray. Fibers and terminals of varying densities were observed in the bed nucleus of the stria terminalis, medial part of the central nucleus of amygdala, external layer of the median eminence, thalamus and central gray. The highest concentrations of helospectin-like immunoreactivity were found in the cerebral cortex, hypothalamus and medulla. The chromatographic analysis of brain extract revealed one major peak with elution properties similar to those of authentic helospectin I. Helospectin-immunoreactive neurons were located in the suprachiasmatic nucleus, central gray, cerebral cortex, dorsomedial hypothalamic nucleus and supramammillary nucleus. Helospectin-immunoreactive fibers and terminals were found in the bed nucleus of the stria terminalis, medial part of the central nucleus of amygdala, median eminence, lateral parabrachial nucleus, central gray, cerebral cortex, thalamus and nucleus of the solitary tract. The present study has revealed novel neuronal systems in the rat brain by using antisera against the lizard peptides helodermin and helospectin. The patterns of immunostaining suggest a role for the helodermin- and helospectin-like peptides in the hypothalamo-hypophyseal control of endocrine functions.

Animals↗

PubMed1992

Lansoprazole and omeprazole have similar effects on plasma gastrin levels, enterochromaffin-like cells, gastrin cells and somatostatin cells in the rat stomach.

This study compares the effects of lansoprazole and omeprazole on the activation and proliferation of enterochromaffin-like (ECL) cells in the rat stomach. Lansoprazole was given orally once daily for 10 weeks in two doses, 135 and 200 mumol/kg. Omeprazole was given by the same regimen in a dose of 400 mumol/kg, which is equipotent in terms of acid inhibition to the higher lansoprazole dose. Lansoprazole (both doses) as well as omeprazole raised the plasma gastrin levels about 11-fold 2 h after dosing and 8-to 10-fold 24 h after dosing, reflecting complete (2 h) and 70-80% (24 h) reductions of gastric acid secretion. Administration of either drug for 10 weeks increased the weight of the stomach and the oxyntic mucosa. The oxyntic mucosal histidine decarboxylase activity, histamine concentration and ECL cell density were increased to the same extent in the rats given either of the two lansoprazole doses or omeprazole. The numbers of antral gastrin cells were doubled and the numbers of antral somatostatin cells half that in the controls. These results show that long-standing lansoprazole-evoked hypergastrinemia affects the ECL cell similarly to omeprazole, ranitidine and other acid secretion inhibitors.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1992

Reinnervation of syngeneic mouse pancreatic islets transplanted into renal subcapsular space.

A syngeneic transplantation of 150 islets into the subcapsular renal space was performed on normoglycemic or alloxan-induced diabetic male C57BL/6 mice. Six, 8, 14, or 20-21 wk after transplantation, the graft-bearing kidney was removed and processed for microscopical examinations with indirect immunofluorescence for neuropeptides and tyrosine hydroxylase, and with acetylcholinesterase staining to visualize nerve fibers within the graft. Six weeks after implantation, only a few scattered nerve fibers were observed within the grafts. A progressive increase in the number of nerves was observed until 14 wk after transplantation, after which, a stable level was reached. Alloxan-induced diabetic mice showed quantitatively and qualitatively similar reinnervation to normoglycemic mice 20 wk after transplantation. The findings demonstrate the presence of sympathetic nerve fibers (containing tyrosine hydroxylase and neuropeptide Y), mainly accompanying ingrowing blood vessels; parasympathetic nerve fibers (containing acetylcholinesterase and vasoactive intestinal peptide), possibly reaching the graft from the adjacent renal capsule; and afferent nerve fibers (containing substance P and calcitonin gene-related peptide), which were less numerous. The data suggest that transplanted islets become reinnervated by ingrowth of nerve fibers from the implantation organ and that several types of nerves are present.

Animals↗

PubMed1992

Antrectomy does not accelerate reversal of omeprazole-induced trophic effects in the rat stomach.

The oxyntic mucosa in the rat stomach is under the influence of circulating gastrin. The histamine-producing enterochromaffin-like (ECL) cells constitute the major endocrine cell population in the oxyntic mucosa. They are notably sensitive to changes in the serum gastrin concentration and respond to long-term hypergastrinemia with hyperplasia, whereas hypogastrinemia induces hypoplasia. In the present study long-term, sustained hypergastrinemia was induced by daily treatment with a high dose of the proton pump inhibitor omeprazole. After 10 weeks omeprazole-treated and control rats were antrectomized, resulting in prompt hypogastrinemia. Antrectomy was followed by a rapid reduction of the thickness of the oxyntic mucosa and a somewhat slower reduction of the ECL cell number in both omeprazole-treated and control rats. The percentage decrease in the ECL cell number with time was similar in both groups; after 2-3 weeks the ECL cell number was half of that before antrectomy in both groups. Interestingly, however, 12 weeks after antrectomy the ECL cell number in the omeprazole-pretreated rats remained elevated compared with untreated rats. The histamine concentration of the oxyntic mucosa was markedly lowered within a week after antrectomy in both omeprazole-treated and control rats. Although antrectomy induces hypogastrinemia and although atrophy develops rapidly in the oxyntic mucosa, the omeprazole-induced ECL cell hyperplasia was not completely reversed by antrectomy during the 12 weeks of examination.

Animals↗

PubMed1992

Somatostatin cells in the oxyntic mucosa of hypo- or hypergastrinemic rats.

The present report describes the long-term effects of antrectomy, antrum exclusion, portacaval shunt, omeprazole treatment, or the combination of omeprazole treatment and portacaval shunt on the number and density of somatostatin cells in the oxyntic mucosa of the rat. Antrectomy, which is associated with hypogastrinemia, raised the number and density of the somatostatin cells, whereas antrum exclusion and omeprazole treatment, which are associated with hypergastrinemia, reduced the number and density of the somatostatin cells. Portacaval shunt, which is associated with hypogastrinemia, increased both the number and the density. Omeprazole treatment of portacaval--shunted rats suppressed or even reversed the somatostatin cell hyperplasia after portacaval shunt alone. From these findings it is unlikely that gastrin stimulates the proliferation of somatostatin cells in the oxyntic mucosa. In fact, there seems to be an inverse relationship between the serum gastrin concentration and the somatostatin cell number.

Animals↗

PubMed1992

Unilateral vagal denervation suppresses omeprazole-induced trophic effects on the denervated side of the rat stomach.

In several experimental animals treatment with large doses of the proton pump inhibitor omeprazole leads to hypergastrinemia and with time to trophic effects in the acid-producing part of the stomach, most notably an increased density of the histamine-producing enterochromaffin-like (ECL) cells. The trophic effects are thought to reflect the increase in circulating gastrin. In the present study unilateral vagal denervation in the rat partly suppressed the tropic effects seen in the denervated side of the stomach but not those in the intact side after treatment with omeprazole for 10 weeks. Unilateral vagal denervation significantly reduced the proliferative stimulus of omeprazole on the ECL cells in the denervated part of the stomach. Thus, an intact vagal innervation appears to be essential for the capacity of the oxyntic mucosa, including the ECL cells, to respond to elevations in serum gastrin. We suggest that gastrin and the vagus interact to maintain trophic control of the oxyntic glands.

Animals↗

PubMed1992

Reversibility of the cell kinetic changes induced by omeprazole in the rat oxyntic mucosa. An autoradiographic study using tritiated thymidine.

Both oxyntic mucosal progenitor cells and enterochromaffin-like (ECL) cells are under the trophic control of gastrin. We studied the effect of discontinuing omeprazole-induced hypergastrinemia on cell proliferation and ECL cell function in the rat oxyntic mucosa. All rats had hypergastrinemia after 16 days' omeprazole administration, and the proliferation rate of both progenitor and ECL cells was increased, whereas it was decreased 5 days after withdrawal of omeprazole. Circulating gastrin had normalized by then. The proliferative activity of the progenitor cells returned to normal within 10 days, whereas that of the ECL cells remained suppressed for at least 20 days. The histidine decarboxylase activity of the ECL cells changed in parallel with their proliferative activity. These data suggest either a down-regulation of membrane receptors or the involvement of still unknown inhibitors of mitotic activity and ECL cell function in the oxyntic mucosa.

Animals↗