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Biomedical subjects

F Sundler

Publications and source records attributed to F Sundler.

At least 181 records · Page 10Linked to original sources
PubMed1993

Islet amyloid polypeptide gene expression in the endocrine pancreas of the rat: a combined in situ hybridization and immunocytochemical study.

The expression of the islet amyloid polypeptide (IAPP) gene within the endocrine pancreas and its correlation with insular neuroendocrine peptide localization were investigated in the rat. In situ hybridization with a 35S-labelled IAPP-mRNA specific oligonucleotide probe was combined with immunocytochemistry. In situ hybridization alone showed strong autoradiographic labelling of the pancreatic islets. In situ hybridization combined with immunocytochemistry for IAPP, revealed labelling of the IAPP-immunoreactive cells. However, when in situ hybridization was combined with immunocytochemistry for proinsulin, we noted a lack of proinsulin immunoreactivity in some peripherally located autoradiographically labelled islet cells. Furthermore, combination of in situ hybridization and immunocytochemistry for somatostatin showed autoradiographic labelling of somatostatin cells to a varying degree. This was further confirmed by showing cellular co-localization of IAPP and somatostatin by immunocytochemical double staining. We conclude that IAPP is mainly synthesized in insulin cells. Additionally, a subpopulation of the somatostatin cells is capable of IAPP synthesis. This may account for the relatively small reduction in the content of IAPP-mRNA in islets compared to the marked reduction of insulin mRNA after streptozotocin-induced diabetes in rats as previously reported.

Amyloid↗
PubMed1993

Effect of omeprazole-evoked hypergastrinemia on ultrastructure of enterochromaffin-like cells in the stomach of portacaval-shunted rats.

The histamine-producing enterochromaffin-like (ECL) cells in the acid-producing portion of the rat stomach responded to long-standing hypergastrinemia (omeprazole treatment daily for 8-10 weeks) with hypertrophy (and hyperplasia) and with a reduced number of granules and vesicles per unit cytoplasm. There was a reduction in the ratio of electron-dense granules versus vesicles and an increase in the profile diameter of the vesicles. Also, portacaval shunting (PCS) induced changes in the ECL cells, manifesting (i) as an increase in cell number and size, and (ii) as a reduced number of granules and vesicles per unit area. The cytoplasmic granules and vesicle profiles were enlarged, and the ratio of granules versus vesicles was reduced. The combination of PCS and long-standing hypergastrinemia (omeprazole treatment) produced a greatly enhanced ECL cell hypertrophy (and hyperplasia) and a marked reduction in the number of granules. The ratio of granules versus vesicles was markedly reduced while the profile diameters of both granules and vesicles were increased. The relative predominance of very large vesicles (vacuoles) was a prominent feature of the ECL cells in these rats.

Animals↗
PubMed1993

Time-dependent changes in enterochromaffin-like cell kinetics in stomach of hypergastrinemic rats.

BACKGROUND: Hypergastrinemia has been claimed to cause first hyperplasia and then dysplasia/neoplasia of enterochromaffin-like (ECL) cells in rat stomach. The growth is thought to reflect an accelerated self replication rate of mature ECL cells. The cytokinetics and the histidine decarboxylase (HDC) activity of the ECL cells were investigated during sustained hypergastrinemia. METHODS: Hypergastrinemia was evoked by omeprazole (400 mumol.kg-1 x day-1 orally) for up to 1 year. Immunocytochemistry for histamine was used to determine the ECL cell density and combined with [H3]-thymidine autoradiography to establish the labeling index (LI), i.e., the proportion of the ECL cells that has incorporated [H3]thymidine. RESULTS: The ECL cell density increased progressively for 10-20 weeks in response to the hypergastrinemia and remained at a plateau for the remainder of the study. The hyperplasia was diffuse with additional micronodules at 52 weeks. The ECL cell Ll was maximally elevated after 1-2 weeks and declined to control values after 10-20 weeks of treatment. In contrast, the HDC activity remained elevated for the duration of the study. CONCLUSIONS: The ECL cell hyperplasia reflects the transiently elevated ECL cell Ll during the early phase but is not associated with an accelerated rate of mitosis during the 10-52 weeks period. Even though with time gastrin seems to loose its ability to sustain a high ECL cell Ll it retains its ability to maintain a high HDC activity.

Animals↗
PubMed1993

Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: immunocytochemical and immunochemical evidence.

Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal peptide-like hypothalamic peptide occurring as two variants, PACAP-27 and the C-terminally extended PACAP-38. Immunoreactive PACAP has also been demonstrated in the enteric nervous system and in the innervation of the respiratory tract. We have examined the possibility that PACAP occurs in the sensory nervous system of the rat. Immunocytochemistry revealed PACAP in numerous nerve fibres in the superficial layer of the dorsal horns of the spinal cord, in nerve cell bodies (most of them of small size) of the spinal ganglia and trigeminal ganglia and in nerve fibres running close to and within the surface epithelium in the skin of the nose, the tongue, the larynx-trachea, and the urinary bladder as well as around the ducts of the submandibular gland. In all locations, PACAP co-existed with calcitonin gene-related peptide and substance P, the PACAP-immunoreactive fibres and cell bodies constituting a subpopulation of those storing substance P and/or calcitonin gene-related peptide. Additional PACAP-immunoreactive fibres not associated with epithelia seemed to lack calcitonin gene-related peptide and substance P. Capsaicin treatment reduced the density of PACAP- and calcitonin gene-related peptide/substance P-immunoreactive fibres in the tissues examined. On the whole, the immunocytochemical results agreed with those obtained by radioimmunoassay for PACAP and CGRP. The data favour a role for PACAP in primary sensory neurons.

Animals↗
PubMed1993

Pituitary adenylate cyclase activating peptide produces a marked and long-lasting depression of a C-fibre-evoked flexion reflex.

Pituitary adenylate cyclase activating peptide (PACAP) is a novel vasoactive intestinal peptide-like peptide. It has a neuronal localization and occurs in two forms, PACAP-38 and the C-terminally truncated PACAP-27. In a recent report we described a dense accumulation of PACAP-27-immunoreactive nerve fibres in the superficial layer of the dorsal horn in the spinal cord and a few PACAP-27-immunoreactive nerve cell bodies in the spinal ganglia in the rat. Double-immunostaining showed that immunoreactive PACAP-27 occurred in a subpopulation of the calcitonin gene related peptide/substance P-containing cell bodies and fibres. In this study, PACAP-27 (0.47-0.63 pmol) given intrathecally produced a significant and long-lasting suppression of C-fibre-evoked flexion reflex produced by the electrical stimulation of the plantar nerve and recorded as a reflex discharge in the peroneal nerve. With a higher dose, 1.25 pmol, the magnitude of the response was not increased further but the effect became longer-lasting. PACAP-38 and vasoactive intestinal peptide were tested in doses up to 5 pmol and produced a significant and, in the case of PACAP-38, long-lasting suppression of the spinal flexion reflex. PACAP-27 seemed to be much more potent than PACAP-38 and vasoactive intestinal peptide. Intrathecal PACAP-27 was without effect on the monosynaptic stretch reflex (evoked by electrical stimulation of the gastrocnemius nerve and recorded as a reflex discharge in the sciatic nerve), suggesting that its effect on the flexion reflex is specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Peptide YY: a neuropeptide in the gut. Immunocytochemical and immunochemical evidence.

Peptide YY immunoreactivity was detected in neuronal elements in the upper digestive tract of the rat, cat, ferret and pig by immunocytochemistry and radioimmunoassay combined with high-performance liquid chromatography. The two peptide YY antisera used do not recognize the related peptides neuropeptide Y and pancreatic polypeptide. In the rat peptide YY-immunoreactive nerve fibres were virtually restricted to the stomach smooth muscle of the minor curvature where they were numerous. Peptide YY-immunoreactive nerve cell bodies occurred in small ganglia on the serosal surface of the minor curvature. In the cat and ferret peptide YY-immunoreactive nerve fibres occurred in the circular smooth muscle layer of both the minor and major curvatures of the stomach and also in the upper small intestine; such fibres were numerous also in myenteric ganglia in these regions. In the pig, they were few but had roughly the same distribution as in the cat and ferret, except that they were quite numerous in thick muscle bundles close to the oesophagogastric junction. The presence of peptide YY-immunoreactive nerve cell bodies within the myenteric ganglia along the upper digestive tract of cat, ferret and pig, and in serosal ganglia of the rat stomach, indicates that at least some of the peptide YY-immunoreactive fibres demonstrated originate in or close to the gut wall. Double-staining experiments revealed that virtually all peptide YY-containing neurons and nerve fibres were distinct from those storing neuropeptide Y. Peptide YY-immunoreactive endocrine cells were encountered not only in the lower intestines but also in the stomach of the four species studied. In the antrum such cells were numerous and constituted a subpopulation of the gastrin-containing cells. In the oxyntic mucosa they were few and contained somatostatin. Radioimmunoassay revealed peptide YY-like peptides in gastric mucosa and smooth muscle from the upper digestive tract of all four species examined. The results of high-performance liquid chromatography suggest that the peptide YY-like material in the upper digestive tract is distinct from neuropeptide Y and pancreatic polypeptide and identical with authentic peptide YY except in the antral mucosa where only a small proportion of the peptide YY-immunoreactive material eluted like authentic peptide YY.

Animals↗
PubMed1993

Peptide-containing neurons remain unaffected after intestinal autotransplantation: an experimental study in the piglet.

The gut is richly supplied with peptide-containing nervous elements. In the present immunocytochemical study the origin, occurrence and topographical distribution of nerves containing vasoactive intestinal polypeptide (VIP), enkephalin, substance P (SP), somatostatin, neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP) and galanin were investigated in the porcine small intestine. In order to study the origin (extrinsic or intrinsic) of the nerve fibers, specimens from autotransplanted and extrinsically denervated jejunum were examined. Furthermore, possible changes in the distribution of intrinsic neurons after extrinsic denervation were studied. In the control jejunum each nerve fiber population had its own characteristic topographic distribution. There was no overt difference in distribution pattern of peptide-containing nerve fibers and cell bodies between the transplanted and the control segment except that NPY-, SP- and CGRP-containing nerve fibers disappeared around blood vessels. Thus VIP-, somatostatin-, GRP-, enkephalin- and galanin-containing nerve fibers were visibly unchanged in the transplanted segment. The results support the view that the peptide-containing nerve fibers are mainly intrinsic in origin except the NPY-, SP- or CGRP-containing perivascular nerve fibers which are extrinsic to the gut wall. In addition, the results of the present study suggest that transplantation and extrinsic denervation have no major effect on the distribution pattern of the intrinsic neuronal systems.

Anastomosis, Surgical↗
PubMed1993

Mucosal exudation of plasma is a noninjurious intestinal defense mechanism.

We have demonstrated in sensitized rats that the immediate response to endointestinal challenge with allergen (10(-6) M ovalbumin) is characterized by mucosal exudation of plasma with little or no concomitant change in the mucosal absorption capacity. The luminal entry of plasma macromolecules also leaves the light microscopic structure and the ultrastructure of the mucosa unaffected. It is possible that the plasticity of epithelial zonulae occludens allows a noninjurious and unidirectional paracellular flux of extravasated plasma into the gut lumen. We propose that inflammatory-stimulus-induced mucosal exudation of plasma belongs to the first-line defense mechanisms of the intact lining of the intestine.

Allergens↗
PubMed1993

Immunohistochemical localization of peripheral nitric oxide synthase-containing nerves using antibodies raised against synthesized C- and N-terminal fragments of a cloned enzyme from rat brain.

Antibodies were raised in rabbits against C- or N-terminal fragments of a cloned nitric oxide synthase (NOS) enzyme from rat cerebellum, and used for demonstration of NOS-immunoreactive (NOS-IR) nerves in different tissues from the rat (colon, duodenum, adrenal gland, aorta, caval vein, penis and urethra). Both antisera demonstrated the same neuronal elements, although with differences in intensity in the immunoreaction in some tissues. Sections incubated with antisera preabsorbed with excess of the antigens showed no NOS immunoreactivity. In duodenum and colon, NOS-immunoreactivity was found in the cytoplasm of numerous cell bodies in myenteric ganglia and in some nerve cell bodies in the submucosa. NOS-IR nerve fibres were numerous in the circular muscle layer, while few were found in the longitudinal layer or the mucosa and submucosa. In the penis, strong NOS immunoreactivity was found in nerves surrounding the deep penile and dorsal arteries, and in nerves in the stroma of the cavernous tissue. In the urethra, NOS immunoreactivity was found in nerves in the mucosa. No NOS immunoreactivity was found in the urothelium. The adrenal medulla, and occasionally the cortex, contained nerve cell bodies with strong cytoplasmic NOS immunoreactivity as well as scattered nerve fibres. No NOS immunoreactivity was found in the abdominal aorta or inferior caval vein. Combined NOS immunostaining and NADPH diaphorase staining showed that virtually all NOS-IR nerve structures were also NADPH diaphorase-positive. However, thin nerve fibres and cell linings were sometimes better visualized by NOS-immunohistochemistry. Furthermore, the adrenal cortex, which only occasionally showed NOS immunoreactivity, was strongly NADPH diaphorase-positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Peptide-containing nerve fibers in human airways: distribution and coexistence pattern.

The occurrence, distribution and coexistence pattern of an array of neuropeptides and tyrosine hydroxylase in the human larynx, trachea, bronchi and lungs were studied by immunocytochemistry. A rich supply of nerve fibers containing vasoactive intestinal peptide (VIP) was seen close to blood vessels, glands and nonvascular smooth muscle. Pituitary adenylate cyclase-activating peptide (PACAP)-containing fibers were numerous among bundles of smooth muscle. Moderate numbers of helospectin-containing nerve fibers were seen in the nonvascular smooth muscle. The majority of neuropeptide Y (NPY)-containing fibers were located in the nonvascular smooth muscle; some fibers also occurred around blood vessels and glands. Substance P (SP) and calcitonin gene-related peptide (CGRP)-containing fibers were generally few and distributed beneath the epithelium, among bundles of smooth muscle, around blood vessels and glands. A conspicuous finding was the lack of SP- and CGRP-containing fibers within the respiratory epithelium. Galanin-containing nerve fibers were moderate in number among bundles of smooth muscle. Tyrosine hydroxylase-containing fibers were numerous around blood vessels and glands. The majority of the VIP-containing nerve fibers present in nonvascular smooth muscle also stored PACAP and helospectin. A subpopulation of VIP-containing fibers in both vascular and nonvascular smooth muscle and around glands stored NPY. Additionally, galanin was found to occur in many VIP-containing fibers located among bundles of smooth muscle.

Adrenergic Fibers↗
PubMed1993

Enterochromaffin-like cells in rat stomach respond to short-term infusion of high doses of cholecystokinin but not to long-term, sustained, moderate hyperCCKemia caused by continuous cholecystokinin infusion or pancreaticobiliary diversion.

The histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa are controlled by gastrin. An acute gastrin challenge induces release and accelerated resynthesis of ECL cell histamine. Long-term stimulation with gastrin causes ECL cell hyperplasia. We set out to study whether the ECL cells respond not only to gastrin but also to cholecystokinin (CCK). A wide dose range of gastrin-14 sulfated and -17 non-sulfated and CCK-8 sulfated (CCK-8s) and non-sulfated (CCK-8) was infused intravenously to rats for 3 h. The activity of the histamine-forming enzyme was measured at termination of infusion. Gastrins and CCK-8s were equally effective in activating the enzyme, whereas sulfated CCK-8 was notably less potent than the other three peptides. Clearly, the receptor responsible for activation of the ECL cells distinguishes poorly between gastrin-17 and CCK-8s, which is in line with the characteristics of the CCK-B receptor. Moreover, neither the response to gastrin-17 nor that to CCK-8s was affected by concomitant infusion of devazepide (200 micrograms/kg/h), a selective CCK-A-receptor antagonist. One group of rats received CCK-8s continuously via a minipump. Another group of rats was subjected to pancreaticobiliary diversion (PBD), which increases the plasma CCK concentration 10- to 20-fold. The rats were killed 7 or 10 weeks later, respectively, and the stomachs were analyzed with regard to mucosal growth and ECL cell hyperplasia. HyperCCKemic rats had increased pancreatic weights but showed no signs of growth stimulation in the stomach and no ECL cell hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Hypercholecystokininemia produced by pancreaticobiliary diversion causes gastrin-like effects on enterochromaffin-like cells in the stomach of rats subjected to portacaval shunting or antrectomy.

Gastrin and possibly cholecystokinin (CCK) control the activity and growth of the histamine-containing endocrine cells, the enterochromaffin-like (ECL) cells, in the oxyntic mucosa of the rat. Portacaval shunting (PCS) is known to activate the ECL cells through as yet unknown mechanisms. PCS also exaggerates the ECL cells' response to gastrin, whereas antrectomy causes hypotrophy and hypoplasia of the ECL cells. A recent study showed that the ECL cells failed to respond to sustained hyperCCKemia caused by pancreaticobiliary diversion (PBD). In the present study we investigated whether PBD-produced hyperCCKemia influenced the effects of PCS or antrectomy on the ECL cells. The results show 1) that hyperCCKemia raised the histidine decarboxylase (HDC) activity of the ECL cells in PCS rats but not in control rats, and the CCK-A receptor blockade failed to prevent the enzyme activation; and 2) that PBD prevented the ECL cell hypoplasia and the decrease in HDC activity induced by antrectomy. The findings suggest that under special circumstances endogenous CCK may stimulate the ECL cells.

Animals↗
PubMed1993

Reinnervation of transplanted pancreatic islets. A comparison among islets implanted into the kidney, spleen, and liver.

Islets transplanted beneath the kidney capsule become reinnervated during the first 3-4 months after implantation by both afferent and efferent nerve fibers. To evaluate the importance of the implantation organ for this process, the present study compared both the degree and the types of nerve fibers reinnervating islets transplanted into the liver, kidney, and spleen. For this purpose, 150 syngeneic islets were grafted under the kidney capsule of C57BL/6 mice. In addition, the same animals were injected with 150 islets into the spleen or liver. All animals were killed 14 weeks after transplantation, after which the graft-bearing organs were processed for indirect immunofluorescence for neuropeptides and tyrosine hydroxylase (TH), and with acetyl cholinesterase (AchE) staining to visualize nerve fibers. Both afferent (containing substance P and/or calcitonin gene-related peptide) and parasympathetic (containing vasoactive intestinal peptide or AchE) nerve fibers were absent from islets implanted into the spleen; an occasional CGRP fiber was seen in islets implanted into the liver; and all these fibers were regularly seen in islets implanted beneath the renal capsule. The islets implanted into the liver or spleen contained a dense network of sympathetic (containing neuropeptide Y and TH) nerve fibers that was often more dense than in the islet grafts under the kidney capsule. One-fifth of islets implanted into the liver were, however, completely devoid of demonstrable nerve fibers. In conclusion, there are marked differences with regard to the pattern of reinnervation of islets transplanted to different implantation sites.

Acetylcholinesterase↗
PubMed1993

Turnover and distribution of cathepsin G in the rat.

The turnover of 125I labelled rat polymorphonuclear leukocyte (PMN) cathepsin G with retained enzymatic activity was followed 180 min after an intravenous injection. The plasma half-life of injected radioactivity was approximately 4.5 min. In the plasma sample 15 min after injection the main part of the radioactivity in a gel filtration eluted at the same volume as 3-iodo-tyrosine (3-IT). After 15 min the liver contained about one third of the injected radioactivity. Radioactivity in all organs declined in the course of time. In the pancreas autoradiography showed labelling at the localization of enzyme granules as soon as 15 min after the intravenous injection of radiolabelled substance. All these results suggest a rapid uptake and degradation of cathepsin G in the liver. The distribution of cathepsin G in tissues analysed in the normal rat were localized to the spleen, lymph nodes, and lung. PMNs were immunohistochemically stained, while in the lung indefinable epithelial cells were stained. When rat PMN cathepsin G was added to normal rat plasma, we could identify 36% bound to alpha 1-macroglobulin (alpha 1M) and 19% bound to alpha 1-inhibitor 3 (alpha 1I3) as judged from analysis of gel filtration chromatography and electroimmunoassay (EIA) with autoradiography.

Animals↗
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↗