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Biomedical subjects

F Sundler

Publications and source records attributed to F Sundler.

At least 307 records · Page 17Linked to original sources

Multiple tachykinin pools in sensory nerve fibres in the rabbit iris.

A population of sensory nerve fibres in the rabbit iris is known to contain calcitonin gene-related peptide and tachykinins, such as substance P and neurokinin A. In the presence of atropine and guanethidine, the isolated iris sphincter responded to electrical stimulation with a contraction that could be abolished by tachykinin antagonists. Capsaicin, known to release tachykinins from sensory fibres, evoked a long-lasting tachykinin-mediated contraction of the iris sphincter. Repeated application of capsaicin led to tachyphylaxis, possibly reflecting depletion of releasable neuronal stores of tachykinins. At this stage, electrical stimulation failed to elicit contraction. The capacity of capsaicin to release neuropeptides from sensory fibres was confirmed by determination of substance P- and calcitonin gene-related peptide-like immunoreactivity in the incubation medium and in the iris tissue. The concentrations of substance P and calcitonin gene-related peptide in the iris after capsaicin exposure were reduced by about 25%. Like capsaicin, bradykinin evoked a tachykinin-mediated contraction and tachyphylaxis. However, after development of tachyphylaxis to bradykinin, electrical stimulation or exposure to capsaicin still evoked tachykinin-mediated contraction, albeit a reduced one compared with the response before bradykinin. Hence, capsaicin completely depletes tachykinin stores releasable by prolonged electrical stimulation, whereas bradykinin exhausts only a sequestered pool. The possibility that tachykinins occur in several releasable pools in sensory nerves was investigated in yet another way: the iris sphincter muscle was stimulated electrically once every 2.5 min over several hours. The contractile response diminished gradually.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coexistence and cooperation between neuropeptide Y and norepinephrine in nerve fibers of guinea pig vas deferens and seminal vesicle.

Fluorescence immunocytochemistry of guinea pig vas deferens and seminal vesicle revealed dense networks of nerve fibers containing both neuropeptide Y (NPY) and dopamine-beta-hydroxylase (DBH), a marker for adrenergic neurons. The effects of norepinephrine (NE) and NPY on the smooth musculature of these organs were studied in vitro. NE inhibited the response to electrical nerve stimulation and increased the basic tension in the vas deferens and contracted the smooth muscle of the seminal vesicle, but had no effect on the contractile response to transmural stimulation in the latter organ. NPY had similar effects on the vas and vesicula, i.e. it inhibited the electrically induced contractions and had no effect on the basic tension. The results suggest a role for NPY as a transmitter that acts before the site of the neuromuscular junction to modulate the release of other transmitters from motor nerve fibers in the smooth musculature.

Animals↗

A mixed endocrine adrenal tumour causing steatorrhoea.

A 60 year old man developed steatorrhoea, weight loss, mild diabetes mellitus, labile hypertension and limb cramps. Raised plasma concentrations of catecholamines, particularly noradrenaline and a computed tomography-scan showing an adrenal tumour strongly suggested a pheochromocytoma. Adrenoreceptor blockade reversed the symptoms, decreased faecal fat, and increased duodenal trypsin to normal concentrations. After adrenalectomy the patient was asymptomatic and there was no steatorrhoea. The blood glucose concentrations became normal. Immunocytochemistry revealed the tumour cells to store large amounts of enkephalin and somatostatin reactive material and moderate amounts of immunoreactive beta-endorphin and dynorphin.

Adrenal Gland Neoplasms↗

Immunoreactive delta sleep-inducing peptide in pituitary adrenocorticotropin/alpha-melanotropin cells and adrenal medullary cells of the pig.

Immunoreactive delta sleep-inducing peptide (DSIP) is known to occur in the central nervous system and in body fluids including cerebrospinal fluid, blood and urine. However, the exact nature of the immunoreactive material demonstrated has been a matter of discussion. In the present study, DSIP-like immunoreactivity was demonstrated in the porcine pituitary and adrenal medulla using radioimmunoassay and immunocytochemistry. In the pituitary, the DSIP-like material was present in a subpopulation of the cells storing adrenocorticotropin and alpha-melanotropin. The DSIP immunoreactive cells in the adrenal medulla were identical with a major population of the noradrenaline-storing cells. High-performance liquid chromatography of tissue extracts revealed one major peak of DSIP-like immunoreactivity which did not coelute with synthetic DSIP. The immunoreactive material may represent N-terminally truncated fragments of DSIP. The present results suggest that the anterior and intermediate lobes of the pituitary and the adrenal medulla are potential sources of DSIP-like peptides.

Adrenal Medulla↗

Distribution and content of neuropeptide Y in the human lower esophageal sphincter.

The occurrence and distribution of neuropeptide Y (NPY) was studied in smooth-muscle specimens from the human lower esophageal sphincter region by immunocytochemistry and immunochemistry. Normal individuals and patients suffering from achalasia or hiatus hernia with severe gastroesophageal reflux were examined. NPY fibers were found within and around smooth-muscle bundles of the longitudinal and the circular muscle layers and within the myenteric ganglia. Smooth-muscle specimens from patients with hiatus hernia and gastroesophageal reflux displayed numerous NPY fibers and an increased content of NPY. Specimens from patients with achalasia contained only few NPY fibers and had a decreased content of NPY as compared to specimens from control patients. Conceivably, NPY may play a role in the regulation of the lower esophageal sphincter.

Adolescent↗

Neuropeptides in the airways: a review.

Nerve fibers containing neuropeptide Y, vasoactive intestinal polypeptide/peptide histidine isoleucine, substance P/neurokinin A (NKA), calcitonin-gene-related peptide (CGRP), and galanin are numerous in the respiratory tract. The fibers derive from several different ganglia such as the superior cervical and stellate ganglia, the jugular-nodose ganglionic complex, small ganglia along the vagus nerve, local ganglionic formations in the tracheal wall, and dorsal root ganglia at the cervical and thoracic level. The fibers surround vascular and nonvascular smooth muscle and seromucous glands and can be seen beneath the surface epithelium. In addition, nerve fibers containing substance P/NKA and CGRP penetrate into the surface epithelium. In some instances, neuropeptides are colocalized with "classic" neurotransmitters such as norepinephrine and acetylcholine; in other cases, several peptides coexist. Many of the neuropeptides affect blood flow, smooth muscle tone, and/or seromucous secretion. Some of them may take part in reflex-mediated responses. However, the lack of specific antagonists makes it difficult to define their functional role in the respiratory tract.

Calcitonin Gene-Related Peptide↗

Neurokinin A and galanin in the thyroid gland: neuronal localization.

The distribution of neurokinin A (NKA) and galanin (GAL) in the thyroid gland of several species was examined with immunocytochemistry. NKA-immunoreactive fibers were observed around blood vessels and follicles in all species examined, whereas GAL-immunoreactive fibers were found in mice and rats only. NKA-containing fibers were more numerous than GAL-containing fibers. All thyroid NKA-containing fibers harbored substance P (SP), and the majority of them stored calcitonin gene-related peptide (CGRP) as well. Most thyroid GAL-immunoreactive fibers contained NKA, SP, and CGRP; in a minor population GAL coexisted instead with vasoactive intestinal peptide. Cervical vagotomy (extirpation of the nodose ganglion) reduced the number of NKA- and GAL-containing fibers in the thyroid by approximately 50%. The jugular ganglion and cervical dorsal root ganglia are fairly rich in GAL-, NKA/SP-, and CGRP-containing cell bodies, which presumably represent the source of GAL-, NKA/SP-, and CGRP-containing fibers in the thyroid. The thyroid ganglion is rich in vasoactive intestinal peptide nerve cell bodies, which presumably project to the thyroid gland; a minor proportion of these cell bodies was found to contain GAL as well. Although the distribution of NKA and GAL fibers in the thyroid suggests that the two peptides are involved in the regulation of local blood flow and follicular cell activity, neither NKA nor GAL had any influence on thyroid hormone release as tested in conscious mice.

Animals↗

Occurrence and distribution of neuropeptides in the human skin. An immunocytochemical and immunochemical study on normal skin and blister fluid from inflamed skin.

The content and distribution of substance P (SP), somatostatin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in human skin were investigated. Radioimmunoassay was performed on pooled tissue samples from several regions (fingers, toes, axillas and thighs) and on tissue fluid from spontaneous blisters on inflamed skin. Immunocytochemical localization showed all peptides examined except somatostatin to be present in nerve fibers. Nerve fibers storing SP and CGRP, which were found to coexist, were mostly present as free nerve endings in the superficial part of dermis and in epidermis. SP/CGRP fibers were most abundant in fingers and toes. VIP fibers and NPY fibers were localized in the deeper parts of dermis around blood vessels and acini of sweat glands. Also fibers containing these neuropeptides were most common in fingertips and toes. VIP occurred in relatively high amounts also in skin from axilla whereas NPY in this region was below detection limit. Immunoreactive somatostatin was found in low concentrations in tissue extracts and was not present in amounts sufficient for reliable immunostaining. Fluid from spontaneous blisters on inflamed skin contained detectable amounts of all neuropeptides.

Adolescent↗

Peptide YY-like immunoreactivity in the central nervous system of the rat.

The concentration of peptide YY (PYY)-like immunoreactivity in rat brain and spinal cord was determined by radioimmunoassay. The highest concentrations were found in the cervical spinal cord (18.1 +/- 1.3 ng/g, mean +/- S.E.M.) and in the medulla oblongata (16.3 +/- 1.5 ng/g). Lower amounts were found in the pons and in the hypothalamus. Chromatographic analysis of the PYY-like immunoreactivity from various regions of the brain revealed 95% of the immunoreactive material to be indistinguishable from synthetic porcine PYY. PYY-immunoreactive nerve cell bodies could be demonstrated by immunocytochemistry in the medulla oblongata of colchicine-treated rats, the largest group of cells being found in the midline area between and partly in the raphe pontis and obscurus nuclei. Another large group of immunoreactive cells was detected more laterally in the medial parts of the gigantocellular reticular nucleus. A few cells, finally, were seen in the dorsal parts of the medulla, including the nucleus of the solitary tract. Varicose nerve fibers displaying PYY immunoreactivity were observed in many parts of the hypothalamus, pons, medulla and spinal cord.

Animals↗

Immunocytochemical evidence for the presence of "mammalian" neurohormonal peptides in neurones of the tapeworm Diphyllobothrium dendriticum.

In the nervous system of the obligatory endoparasite Diphyllobothrium dendriticum immunoreactivity (IR) to growth hormone-releasing factor (GRF), peptide histidine isoleucine (PHI), bovine pancreatic polypeptide (BPP), gastrin, gastrin-releasing peptide (GRP), oxytocin, FMRFamide (FMRF) and serotonin (5HT) was demonstrated by immunocytochemical methods. A very strong GRF-IR was observed in the CNS and PNS of larvae and of the constantly growing adult worms. GRF-IR axon terminals occur beneath the basal lamina of the tegument along the inside of the bothridia, the holdfast organ of the worm. GRF-IR fibres surround the yolk producing vitelline glands and occur in the wall of the vagina. PHI-IR was observed in the CNS and PNS of larvae and adult worms. PHI-IR terminals occur beneath the basal lamina of the tegument along the strobila, the nutrient absorbing surface of the worm. PHI-IR fibres seem to innervate the testicular follicles. FMRF-IR fibres and perikarya occur close to the vitelline glands and the uterine pore and in the male copulatory organ. Numerous large 5HT-IR perikarya with long varicose fibres were observed in the nervous system of the worm. 5HT-IR perikarya occur close to the genital atrium. D. dendriticum is the phylogenetically lowest organism in which IR to PHI has been demonstrated.

Animals↗

Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies.

Antibodies to histamine were used to examine the localization of the amine in cells of the stomach and upper small intestine of a great variety of species, including cartilaginous and bony fish, amphibia, reptiles (lizard), birds (chicken) and a large number of mammals. In all species gastric histamine was localized in endocrine cells (invariably found in the epithelium) and mast cells (usually with an extra-epithelial localization). The endocrine cells were identified as such by immunostaining with antibodies to chromogranin A and the mast cells were identified by toluidine blue staining. Histamine-immunoreactive endocrine cells were found almost exclusively in the acid-producing part of the stomach; only rarely were such cells observed in the pyloric gland area. They were fairly numerous in the gastric mucosa of the two subclasses of fish as well as in the amphibia and reptile species studied. Here, the majority of the histamine-immunoreactive endocrine cells seemed to have contact with the gastric lumen (open type cells) and were located in the surface epithelium (certain fish only) or together with mucous neck cells at the bottom of the pits. In the chicken, histamine-immunoreactive endocrine cells were numerous and located peripherally in the deep compound glands. They were without contact with the lumen (closed type) and had long basal extensions ("paracrine" appearance), running close to the base of the oxyntic-peptic cells. In mammals, the number of histamine-immunoreactive endocrine cells in the stomach varied greatly. They were particularly numerous in the rat and notably few in the dog, monkey and man. In all mammals, the histamine-immunoreactive endocrine cells were of the closed type and located basally in the oxyntic glands. They often had a "paracrine" appearance with long basal processes. Histamine-storing mast cells, finally, were few in both subclasses of fish as well as in the amphibian species and in the lizard. They were fairly numerous in chicken proventriculus (beneath the surface epithelium), few in the oxyntic mucosa of mouse, rat and hamster, moderate in number in hedgehog, guinea-pig, rabbit, pig and monkey, and numerous in cat, dog and man.(ABSTRACT TRUNCATED AT 400 WORDS)

APUD Cells↗

Existence and coexistence of peptides in nerves of the mammalian ovary and oviduct demonstrated by immunocytochemistry.

The immunocytochemical distribution of substance P (SP), gastrin releasing peptide (GRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), and neuropeptide Y (NPY) was studied in the ovary and the Fallopian tube (oviduct) of rats, guinea-pigs, cows, pigs and humans. Generally, the nerve supply was better developed in the oviduct than in the ovary. GRP fibers were most scarce in all tissues. Nerves containing SP were particularly numerous in the oviduct of rat and guinea-pig, supplying the muscular wall and blood vessels. VIP and PHI coexisted in dense plexuses of nerves, not only around blood vessels but also in the follicular wall and the interstitial gland of the ovary, as well as within the smooth muscle layers and subepithelially in the oviduct. The general distribution of NPY was similar, but these immunoreactive nerves were even more numerous. Sequential staining for dopamine-beta-hydroxylase and NPY together with results of chemical sympathectomy with 6-hydroxydopamine suggested that NPY was stored in the noradrenergic sympathetic nerves.

Animals↗

Regulatory peptides in lower esophageal sphincter of pig and man.

Smooth muscle specimens from the lower esophageal sphincter (LES) region of pig and man were analyzed for vasoactive intestinal peptides (VIP), substance P (SP), enkephalin, neuropeptide Y (NPY), gastrin/cholecystokinin (CCK), neurotensin, and somatostatin using immunocytochemistry and radioimmunoassay. VIP-, SP-, enkephalin-, and NPY-immunoreactive nerve fibers were observed in the LES of both species, whereas nerve fibers containing gastrin/CCK, neurotensin, and somatostatin could not be demonstrated. The peptide-containing nerve fibers occurred in the intramural ganglia and in the smooth muscle layers. There was a rich supply of VIP- and NPY-immunoreactive fibers, whereas the supply of SP- and enkephalin-immunoreactive nerve fibers were moderate in number in both species examined. The concentration of VIP, SP, enkephalin, and NPY was comparable in the two species. The present study shows that the pattern of peptidergic innervation of the LES is similar in pig and man. It is proposed that neuronal VIP, SP, enkephalin, and NPY may serve to modulate the motor activity of the LES and that the pig is a suitable experimental animal for the study of regulatory peptides and LES functions.

Adult↗

Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats.

Unoperated female rats were subjected to daily oral treatment with omeprazole (10 or 400 mumol/kg body wt), ranitidine (175 + 175 + 350 mumol/kg body wt), or vehicle and antrectomized rats were treated with omeprazole (400 mumol/kg body wt) or vehicle. After 10 wk of treatment, plasma gastrin levels were high in unoperated rats treated with the high omeprazole dose and with ranitidine, and low in antrectomized controls. Plasma gastrin levels were slightly higher in the low-dose omeprazole group than in the intact controls. In antrectomized rats treated with the high dose of omeprazole, the plasma gastrin level was in the same range as in intact control rats. A close correlation (r = 0.89, p less than 0.0001) was found between the plasma gastrin level and the oxyntic mucosal enterochromaffinlike cell density (as well as the tissue levels of histidine decarboxylase and histamine in the oxyntic mucosa) in all groups. The somatostatin cell density in the oxyntic mucosa was not altered by the various treatments. During a recovery period of 10 wk after the 10-wk treatment, the enterochromaffinlike cell density and histamine concentration decreased by 30%-40% in the rats treated with the high dose of omeprazole, whereas the corresponding values increased by 50% and 40%, respectively, in the control rats. The difference between the two groups, however, was still statistically significant. Plasma gastrin levels and gastric histidine decarboxylase activity returned to control values during recovery. The results suggest that the observed changes in enterochromaffinlike cell density are related to the plasma gastrin levels and that they are reversible. it is concluded that neither omeprazole nor ranitidine per se is likely to induce proliferation of enterochromaffinlike cells.

Animals↗

Neuronal localization and motor effects of gastrin-releasing peptide (GRP) in rat uterus.

All parts of the internal female reproductive tract of the rat contained nerve fibers with immunocytochemically visible gastrin-releasing peptide (GRP)-like material. GRP-like immunoreactivity was also seen in nerve cell bodies of the paracervical ganglion formation, which in addition, harboured GRP nerve fibers. Pharmacological experiments were performed on isolated uterine and cervical smooth muscle tissue from two groups of spayed animals, one of which received estradiol. Both GRP and its non-mammalian counterpart, bombesin, evoked concentration-dependent clonic contractions in uterus and cervix, most pronounced in the estrogen-treated animals. Bombesin induced a stronger contractile force than GRP. The responses were not affected by tetrodotoxin. The observations suggest that GRP may be one of several neural messengers involved in the control of uterine motor activity.

Animals↗