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Biomedical subjects

F Sundler

Publications and source records attributed to F Sundler.

At least 361 records · Page 20Linked to original sources

Endocrine cells and parietal cells in the stomach of the developing rat.

Gastrin-immunoreactive cells were fairly numerous in the pancreas and upper duodenum of the rat at about the time of birth. A minor population of these cells stained with antibodies directed against the N-terminal region of gastrin-34 as well as with antibodies directed against the C-terminal region. The remainder of the cells stained with the C-terminally directed antibodies only. Within a fortnight after birth all gastrin-immunoreactive cells disappeared from the pancreas and were greatly reduced in number in the duodenum; those that remained were probably CCK cells. Gastrin cells were rare in the antrum at birth and remained rare during the first days after birth. They increased in number, slowly until after weaning (15-20 days of age) and then more rapidly, until 25-30 days of age when the gastrin cell density reached that in adult rats. At the time of birth the gastrin concentration in serum was low; the subsequent increase during the first 2 weeks paralleled the development of the antral gastrin cell system. Adult postprandial serum gastrin concentrations were reached 12 days after birth. Somatostatin cells were rare in both the antral and oxyntic mucosa at birth. They increased gradually in number until about a month after birth when the cell density reached that seen in adult rats. In the oxyntic mucosa the ECL and A-like cells are the predominant endocrine (argyrophil) cell types. They were not detected until about 4 days after birth. Their number increased slowly until about 30 days of age. They did not stain argyrophil until about 2-4 weeks after birth. Parietal cells were few at birth; ultrastructurally they appeared to be in an active state and histochemically they were shown to contain carbonic anhydrase. The pH of the gastric content of newborn rats was close to 5; 15-17 days after birth the pH was about 4 in freely fed rats. In fasted rats shortly after birth the pH was about 4. Two weeks later it was around 2, which is the pH measured in older rats. Hence, the full capacity for acid secretion is probably not established until weaning. Fasting greatly lowers the serum gastrin concentration and the histidine decarboxylase activity of the ECL cells in adult rats. Before weaning, fasting produced these effects only to a minor degree.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Effects of portacaval shunt on the rat stomach.

In portacaval-shunted rats, basal but not pentagastrin-stimulated acid secretion was higher than in sham-operated controls. The basal serum gastrin concentration was unchanged and the postprandial serum gastrin concentration lowered following portacaval shunt. Thus, gastrin is not responsible for the elevated basal acid secretion. The present study provides evidence that there is no trophic effect on the oxyntic mucosa as a whole and that there is no change in parietal cell-associated gastrin receptors after portacaval shunting. Interestingly, however, endocrine cells in the oxyntic mucosa (the histamine-containing ECL cells) proliferated greatly and the pentagastrin- and cholecystokinin octapeptide-induced activation of the histamine-forming enzyme, histidine decarboxylase, in these cells was much greater than in control rats. Analysis of the dose-response curves for the enzyme-activating effect of pentagastrin and cholecystokinin-octapeptide indicated that the D50 values for these two stimulants were not altered by shunting but that the maximal enzyme activation was greatly elevated. The enhanced enzyme activation can be partly, but not fully, explained by the fact that the ECL cells were increased in number. The enhanced response following portacaval shunt probably reflects also an increased number of gastrin receptors per ECL cell. The effect of portacaval shunting on gastric ECL cells can perhaps be explained by impaired degradation in the liver of intestinal substance(s) exerting a highly specific trophic effect on the ECL cells or, alternatively, causing an enrichment of gastrin receptors on these cells, thereby making them more sensitive to the trophic effect of gastrin. The ECL cell hyperplasia is manifest about 4 weeks after the shunting. A modified procedure for portacaval shunting which left the gastroduodenal vein (otherwise ligated) drained to the liver produced the same trophic effect as conventional portacaval shunt, suggesting an intestinal rather than gastroduodenal origin of the agent(s) responsible for the trophic action.

Animals↗

Pancreatic polypeptide-producing tumors. Report on two cases.

Histochemical, chemical and clinical features of two malignant endocrine pancreatic tumors were studied. Both tumors contained pancreatic polypeptide (PP)-immunoreactivity in the majority of tumor cells. In addition, one tumor contained a few scattered serotonin-fluorescent cells and the other scattered gastrin-immunoreactive cells. Pancreatic polypeptide hypersecretion was established from both tumors. Serotonin was produced by one tumor and gastrin was secreted by the other. No PP-associated endocrine symptoms were present, whereas the hypergastrinemia may have caused a bleeding duodenal ulcer in one patient. Although both tumors were highly malignant the clinical courses in the two patients were very different; one patient died within a few months whereas the other is alive 2 years after the diagnosis.

Adult↗

Is substance P necessary for corneal nociception?

Substance P (SP)-containing nerve fibers are few in the rabbit cornea, which is richly supplied with acetylcholinesterase-positive nerve fibers, presumably sensory in nature. Treatment with capsaicin given by retrobulbar injection 48 h prior to sacrifice caused SP to disappear from the SP nerves in the cornea without affecting the acetylcholinesterase-positive nerve fibers. The corneal sensitivity to a tactile stimulus (wetted cotton swabs) and to a chemical stimulus (local application of capsaicin) and the disruption of the blood-aqueous barrier after local injury (infrared irradiation of the iris) were tested after pretreatment with capsaicin (retrobulbar injection) the SP antagonist [D-Pro2,D-Trp7,9]SP (single topical application or long-term application twice daily for 2 months), the local anaesthetic oxibuprocaine (topical application), or the neuronal blocker tetrodotoxin (intravitreal injection). All these treatments abolished or reduced the disruption of the blood-aqueous barrier after local injury but only oxibuprocaine and tetrodotoxin abolished the corneal sensitivity to tactile and chemical stimuli. It is suggested that SP nerve fibers constitute a minor proportion of the sensory nerve supply to the cornea, that the neurogenic mechanisms involved in the response to ocular injury differ from those involved in corneal nociception, and that uveal SP is involved in the response to ocular trauma and that corneal SP is probably not necessary for corneal nociception.

Anesthetics, Local↗

Distribution of serotonin-containing neurons and their pathways in the supraoesophageal ganglion of the cockroach Periplaneta americana (L.) as revealed by immunocytochemistry.

The distribution of serotonin (5-HT)-containing neurons in the supraoesophageal (cerebral) ganglion of the cockroach Periplaneta americana was studied using immunocytochemistry and the formaldehyde histofluorescence method ( Klemm , '83). In this material immunocytochemistry was more sensitive than the formaldehyde histofluorescence procedure. A relatively small number of 5-HT-immunoreactive cell bodies (220-280) were found. For the first time, their processes could be followed. They highly arborize and innervate many brain regions. Three patterns of monoamine innervation have been demonstrated: (1) 5-HT and catecholamine fibres ( Klemm , '83) occurring in the same region (e.g., outer lateral protocerebral neuropil, stratum caudale , mushroom body, fan-shaped body, olfactory lobe), but having certain differences with respect to the organization of their projection fields; (2) 5-HT fibres innervating a region lacking catecholamine-containing fibres (pons); and (3) catecholamine neurons innervating a region lacking 5-HT fibres (ellipsoid body). In the mushroom body only the extrinsic neurons contain 5-HT immunoreactivity. They form a commissural fibre system linking the left- and right-hand mushroom bodies and other brain regions. The pons is part of a 5-HT-neuron fibre system innervating many areas including the mushroom bodies. The present study demonstrates novel, complex, and widely distributed connections within the insect brain.

Animals↗

Occurrence and distribution of neuropeptide-Y-immunoreactive nerves in the respiratory tract and middle ear.

Nerve fibres displaying neuropeptide-Y (NPY) immunoreactivity are abundantly distributed in the respiratory tract of cats, guinea-pigs, rats and mice. Fine beaded NPY fibres were seen in whole-mount spreads of the middle-ear mucosa. In the nasal mucosa and in the wall of the Eustachian tube NPY fibres were numerous around arteries and arterioles but sparse in the vicinity of veins; single fibres were found close to the acini of seromucous glands. In the tracheobronchial wall NPY fibres occurred in the proximity of blood vessels, in the subepithelial layer and in the smooth muscle. Surgical and chemical (6-hydroxydopamine treatment) sympathectomy resulted in disappearance of adrenergic and NPY-containing nerve fibres in the nasal mucosa. Sequential staining with antibodies against dopamine-beta-hydroxylase (DBH) and NPY revealed that DBH and NPY occur in the same perivascular nerve fibres in the nasal mucosa. The distribution of NPY fibres in the respiratory tract suggests multiple functions of NPY, such as regulation of local blood flow, glandular secretion and smooth muscle activity.

Adrenergic Fibers↗

Neuronal cholecystokinin, gastrin-releasing peptide, neurotensin, and beta-endorphin in the intestine of the guinea pig. Distribution and possible motor functions.

The guinea-pig intestine was found to harbor nerve fibers containing immunoreactive cholecystokinin (CCK), gastrin-releasing peptide (GRP), neurotensin or beta-endorphin. Such fibers occurred in the myenteric and submucous ganglia and in the smooth muscle. GRP- and CCK-fibers, in addition, were found in the mucosa. Following colchicine treatment, neuronal perikarya in the myenteric ganglia displayed CCK-, GRP-, or beta-endorphin immunoreactivity. CCK-immunoreactive perikarya were located also in the submucous ganglia. Neurotensin-immunoreactive cell bodies could not be detected. The presence of immunoreactive neuronal perikarya in intramural ganglia indicates that CCK-, GRP- and beta-endorphin-containing fibers are intrinsic to the gut wall. GRP, neurotensin, and beta-endorphin were identified in extracts of smooth muscle by immuno-chemical and chromatographic analysis. CCK-8, GRP and neurotensin contracted the isolated taenia coli. Tetrodotoxin reduced the response to CCK-8 but not that to GRP and neurotensin, suggesting that the two latter peptides act directly on smooth muscle receptors. The effect of CCK-8 is partly mediated by cholinergic nerves, since not only tetrodotoxin but also atropine greatly reduced the CCK-8-induced contractile response. The substance P (SP) antagonist, (D-Pro2, D-Trp7,9)-SP1-11 had no effect on the CCK-8-induced contraction of the taenia. CCK-8 enhanced the SP-mediated (atropine-resistant) contractile response to electrical stimulation but not that mediated by acetylcholine. beta-Endorphin had no effect on the tension of the muscle but reduced the response to electrical stimulation (cholinergic as well as SP-mediated) through a naloxone-sensitive mechanism. While CCK-8 and beta-endorphin seem to play neuromodulatory roles in the taenia coli, the significance of GRP and neurotensin remains enigmatic.

Animals↗

Occurrence and distribution of GRP-immunoreactive nerve fibres in the respiratory tract.

The occurrence and distribution of nerve fibres containing gastrin-releasing peptide (GRP) were investigated in the respiratory tract of several mammals using immunocytochemistry. A moderate supply of nerve fibres displaying GRP immunoreactivity was seen in the middle ear mucosa, the nasal mucosa and the tracheobronchial wall. Generally, the fibres were distributed around blood vessels and seromucous glands. In addition, scattered GRP fibres were seen in the smooth muscle of the tracheal wall. The distribution of GRP fibres in the respiratory tract suggests multiple functions of GRP such as regulation of local blood flow, glandular secretion and smooth muscle activity.

Animals↗

Coexistence of peptide YY and glicentin immunoreactivity in endocrine cells of the gut.

Endocrine cells containing peptide YY (PYY) were numerous in the rectum, colon and ileum and few in the duodenum and jejunum of rat, pig and man. No immunoreactive cells could be detected in the pancreas and stomach. Coexistence of PYY and glicentin was revealed by sequential staining of the same section and by staining consecutive semi-thin sections. Since the PYY sequence is not contained in the glucagon/glicentin precursor molecule the results suggest that the PYY cell in the gut expresses two different genes coding for regulatory peptides of two different families.

Animals↗

Vasoactive intestinal peptide and substance P in salivary glands of the rat following denervation or duct ligation.

Immunoreactive vasoactive intestinal peptide (VIP) and substance P (SP) were studied in parotid, submaxillary and sublingual glands of the rat. The concentration of VIP was highest in the submaxillary gland and lowest in the parotid gland. The concentration of SP was highest in the parotid gland; it was at, or below the limit of detection in the sublingual gland. In the parotid gland the total amounts of VIP and SP were reduced by 95% after parasympathetic denervation (section of the auriculo-temporal nerve). In the submaxillary gland the total amounts of the peptides were unchanged after parasympathetic decentralization (section of the chorda-lingual nerve). In this gland the total amount of SP was reduced by 92% and that of VIP by 50%, when the chorda tympani nerve fibres were cut deep into the hilum. Cutting the nerve fibres at the hilum left the total amounts of the peptides unchanged in the submaxillary gland, whereas in the sublingual gland the total amount of VIP was reduced by 70%. Sympathetic denervation did not reduce the total amounts of the peptides. Duct ligation caused gland atrophy. In the parotid gland the total amounts of VIP and SP were reduced by 40%. In the submaxillary gland the same percentage reduction occurred with regard to SP; however, the total amount of VIP was reduced by 99%. The VIP- and SP-containing nerve fibres reach the salivary glands by the parasympathetic nerves. In both submaxillary and sublingual glands a certain fraction of VIP originates within the glands.

Animals↗

VIP and PHI coexist with an NPY-like peptide in intramural neurones of the small intestine.

Vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI) and neuropeptide Y (NPY) are neuropeptides present in all layers of the small intestine. NPY-immunoreactive fibres in the gut seem to derive from two sources. One population is of extramural (sympathetic) origin and contains noradrenaline, another is of intramural origin and does not contain noradrenaline. In the present study of mouse, rat and pig, immunocytochemistry showed immunoreactive PHI to coexist completely with immunoreactive VIP. This was predictable, since VIP and PHI derive from the same precursor. In addition, however, VIP and PHI were found to coexist with immunoreactive NPY in non-adrenergic (but not in adrenergic) nerve fibres and nerve cell bodies. This coexistence was unexpected, since the VIP precursor does not contain NPY-like sequences.

Animals↗

Immunocytochemical localisation of the icosapeptide fragment of the PP precursor: a marker for 'true' PP cells?

Antisera were raised against the icosapeptide fragment of the pancreatic polypeptide (PP) isolated from the canine pancreas. They were used for the immunocytochemical study of the cellular localisation and distribution of the icosapeptide in the gut and pancreas of various mammals. The results indicate that PP and the icosapeptide coexist in the majority of the PP-immunoreactive cells in the pancreas of cat, dog, pig, monkey and man and in all the PP-immunoreactive cells in the stomach of the cat and dog. The icosapeptide does not seem to occur in cells or nerves containing PP-related peptides, such as peptide YY or neuropeptide Y. PP-immunoreactive cells devoid of the icosapeptide could be demonstrated in the large intestine. These cells are probably distinct from the pancreatic PP cell type, and the PP-immunoreactive material probably represents the homologous peptide YY rather than PP. The present findings support the view that the icosapeptide is part of the PP precursor and hence, only the cells containing immunoreactive icosapeptide in addition to immunoreactive PP are to be considered 'true' PP cells. The icosapeptide antisera did not stain PP cells in mouse, rat and guinea-pig, suggesting marked species variation in the amino acid sequence of the icosapeptide portion of the PP precursor.

Animals↗

Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers.

Neuropeptide Y (NPY)-immunoreactive nerve fibers were numerous around arteries and few around veins. NPY probably co-exists with noradrenaline in such fibers since chemical or surgical sympathectomy eliminated both NPY and noradrenaline from perivascular nerve fibers and since double staining demonstrated dopamine-beta-hydroxylase, the enzyme that catalyzes the conversion of dopamine to noradrenaline, and NPY in the same perivascular nerve fibers. Studies on isolated blood vessels indicated that NPY is not a particularly potent contractile agent in vitro. NPY greatly enhanced the adrenergically mediate contractile response to electrical stimulation and to application of adrenaline, noradrenaline or histamine, as studied in the isolated rabbit gastro-epiploic and femoral arteries. The potentiating effect of NPY on the response to electrical stimulation is probably not presynaptic since NPY affected neither the spontaneous nor the electrically evoked release of [3H]noradrenaline from perivascular sympathetic nerve fibers.

Animals↗

GRP neurones in the rat small intestine issue long anal projections.

Gastrin releasing peptide (GRP) immunoreactive nerve fibres are numerous in the gut wall. Nerve cell bodies containing GRP are regularly found in the myenteric ganglia. The projections of GRP neurones in the rat small intestine were studied after myectomy or transection of the gut wall. Operated rats were left for 8-10 days or 5 weeks. Specimens were studied by immunocytochemistry, immunochemistry and in vitro for motor activity. GRP fibres were absent and GRP was markedly reduced in the gut wall underlying the area of myectomy and 10 mm anally to the myectomy or site of transection. Further anally, GRP and the GRP fibres gradually returned and were back to normal 25-30 mm from the lesion. Myenteric GRP neurones in the rat small intestine thus project anally over a distance of approximately 20-25 mm. A series of experiments was performed in order to test the idea that GRP is directly involved in intestinal motor functions. The results did not support this view. Strips of longitudinal smooth muscle with adherent myenteric ganglia were taken orally and anally to the myectomy and the motor activity of the specimens was compared. Electrical stimulation evoked a contractile response in the oral segment that was 6 times greater than that of the anal segment. However, GRP (10(-9)-10(-5) M) did not evoke contraction and the electrically induced contractile response was unaffected by GRP but could be blocked by atropine. The reduced contractile response in the 'denervated' anal segment is thus probably not due to a shortage of GRP fibres.

Animals↗

Human pancreatic icosapeptide: isolation, sequence, and immunocytochemical localization of the COOH-terminal fragment of the pancreatic polypeptide precursor.

In dogs, the COOH-terminal part of the pancreatic polypeptide precursor gives rise to a stable icosapeptide product against which an antiserum has been raised. By immunohistochemistry, icosapeptide immunoreactivity was localized in human pancrease exclusively to cells that also stored pancreatic polypeptide. Analytical peptide chemistry demonstrated that a peptide corresponding to the canine icosapeptide could be extracted from the pancreatic polypeptide-rich duodenal part of the human pancreas. The human pancreatic icosapeptide was isolated by acid ethanol extraction, gel filtration, anion-exchange chromatography, and reverse-phase high-performance liquid chromatography. The COOH-terminal sequence of the human icosapeptide is very similar to that of the canine icosapeptide, whereas none of the first nine amino acid residues are identical. When the primary structure of peptides from three different species are compared, it is apparent that the pancreatic polypeptide part of the common precursor is a well-conserved sequence as compared to the icosapeptide part, although 8 out of 11 residues in the COOH-terminal sequence of the icosapeptide are identical in all three species.

Amino Acid Sequence↗

Neuropeptide Y in the thyroid gland: neuronal localization and enhancement of stimulated thyroid hormone secretion.

Nerve fibers displaying neuropeptide Y (NPY) immunoreactivity occurred around blood vessels and follicles in the thyroid gland of several mammals, including man. Removal of the superior cervical ganglia or chemical sympathectomy (6-hydroxydopamine treatment) markedly reduced the number of NPY-containing nerve fibers in the thyroid and eliminated norepinephrine-containing fibers. NPY-immunoreactive nerve cell bodies were numerous in the superior cervical ganglia of mouse, rat, and guinea pig. Not unexpectedly, therefore, immunocytochemistry involving sequential staining with antibodies against dopamine-beta-hydroxylase (an enzyme marker for adrenergic neurons) and NPY revealed that most of the NPY fibers were adrenergic. As tested in mice in vivo, NPY did not affect basal or norepinephrine-stimulated thyroid hormone secretion, but enhanced isoprenaline-, TSH-, and vasoactive intestinal polypeptide-induced iodothyronine release. These findings suggest a modulatory role for NPY in the control of thyroid hormone secretion.

Animals↗

Immunocytochemical studies of the peptidergic innervation of the thyroid gland in the Brattleboro rat.

An indirect immunofluorescence technique was used to study the peptidergic innervation of the thyroid gland in homozygous Brattleboro rats (DI) and normal Long-Evans rats (LE). The primary goal of this study was to determine whether the previously demonstrated decrease in thyroid responsiveness to TSH in DI might be due to an abnormality in the innervation of the thyroid. Thyroids from both types of rats were found to contain nerve fibers containing immunoreactivity for vasoactive intestinal peptide (VIP), substance P (SP), neuropeptide Y (NPY), and peptide HI (PHI). All four types of fibers were found in close association with both follicle cells and blood vessels. Well developed networks of fibers surrounding blood vessels were particularly apparent in the case of NPY. The density of fibers associated with follicle cells in DI was at least as great as that in LE in regard to SP, NPY, and PHI. Fibers containing VIP were found in greater abundance in DI than in LE. Additional studies revealed no evidence of thyroid fibers containing either somatostatin or neurophysin, which was used as a marker for vasopressin. We conclude that the reduced responsiveness of the thyroid in DI is not due to an inadequate supply of any of the neuropeptides included in this study. Since VIP is known to enhance thyroid secretion, we suggest that the apparent proliferation of VIP-containing fibers in DI may be a reflection of a neural mechanism attempting to compensate for a thyroid gland deficiency analogous to the humoral mechanism by which TSH secretion increases in response to thyroid deficiency.

Animals↗