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Biomedical subjects

E Brodin

Publications and source records attributed to E Brodin.

At least 127 records · Page 7Linked to original sources
PubMed1983

Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs.

The origin of substance P (SP)-immunoreactive neurons in the lower respiratory tract, esophagus and heart of guinea-pigs was demonstrated by surgical denervation or capsaicin pretreatment with subsequent determination of the tissue levels of SP by radioimmunoassay. In other experiments the effect of vagal nerve stimulation on the SP levels in these tissues was studied. The effects of capsaicin-sensitive afferents in the respiratory tract mucosa and bronchial smooth muscle was also studied by analysis of vascular permeability to Evans blue and insufflation-pressure changes. Our present data indicate that all SP nerves in the trachea and lung are afferent and capsaicin-sensitive. The trachea and stem bronchi receive SP afferents mainly from the right vagus nerve with cell bodies located in both the nodose and jugular ganglia. The SP innervation of the lung seems to have a dual origin: 1. Afferents from both vagal nerves with a crossed type of innervation pattern. 2. A non-vagal source which consists of about 40% of the SP nerves in the lung. These nerves probably originate from thoracic spinal ganglia. The effects of ether and capsaicin on insufflation pressure and increase in vascular permeability were dependent on the integrity of capsaicin-sensitive afferents of both vagal and non-vagal origin. In the guinea pig, systemic capsaicin pretreatment to adult animals seemed to result in irreversible changes in the respiratory tract, while in the rat a successive recovery of the functional response of capsaicin-sensitive afferents occurred. Different regimes of systemic capsaicin pretreatment induced different effects on the cholinergic (atropine-sensitive) insufflation-pressure response. Capsaicin pretreatment, using multiple injections over two days, depressed the cholinergic insufflation-pressure increase, while the cholinergic vagal component was unaffected in animals which received a single dose of capsaicin or local pretreatment with capsaicin on the vagal nerves. The local treatment was more effective with regard to SP depletion in target areas when using alcohol as solvent than when capsaicin was dissolved in paraffin oil, while the functional deficits were similar. The SP nerves in the esophagus were mainly of vagal afferent origin, while the heart atrium seemed to have a dual innervation by both vagal and non-vagal SP nerves.

Animals↗
PubMed1983

Substance P-containing nerve fibers are numerous in human but not in feline intestinal mucosa.

The regional and topographic distribution of substance P-containing nerve fibers in the human and feline intestinal wall was studied by immunocytochemistry and radioimmunoassay. The concentration of substance P was measured in the different layers of the duodenum, jejunum, ileum, and colon. In both humans and cat, substance P fibers were fairly numerous, and the substance P concentration was comparatively high in the smooth muscle layer, including the myenteric ganglia. In humans, but not in cat, substance P fibers were numerous, and the substance P concentration was also high in the mucosa. Substance P-containing nerve cell bodies were observed in the myenteric ganglia of both species. In the submucous ganglia, such nerve cell bodies were seen in the human intestine only, suggesting that they represent the origin of the numerous mucosal substance P fibers in this species. Previous studies have revealed a relative paucity of substance P fibers in the intestinal mucosa of several mammals, such as mouse, rat, and pig. The cat can now be added to those having few mucosal substance P fibers, whereas humans seem to be notably rich in such fibers, suggesting that substance P may play a role in the regulation of mucosal functions in the human intestine.

Adult↗
PubMed1983

Potassium evoked in vivo release of substance P in rat caudate nucleus measured using a new technique of brain dialysis and an improved substance P-radioimmunoassay.

Semipermeable tubules were implanted in rat caudate nucleus in vivo. The tubules were perfused with artificial cerebrospinal fluid and the dialysates collected in fractions which were analysed for substance P content by a sensitive radioimmunoassay (detection limit: 0.1 fmol SP per sample). During controls periods no or comparatively small amounts of SP could be detected in the dialysates. An increase of the potassium concentration in the perfusion fluid to 100 mM or 200 mM induced a release of SP which tended to be concentration dependent. The present results demonstrate a new method to measure in vivo release of SP in rat brain.

Animals↗
PubMed1982

Characterization of two substance P antisera.

The cross reactivity of two currently used substance P (SP) antisera (K 16 and K 25) with various analogues of SP, partial sequences of SP and other naturally occurring peptides were tested in a radioimmunoassay system. Both antisera were found to be C-terminal directed, this tendency being most pronounced for antiserum K 16. The capacity of antiserum K 25 to bind various SP-related peptides correlated to the previously described biological activity of these peptides on the isolated guinea pig ileum. The results thus indicate that this antiserum binds to a biologically active part of the SP-molecule.

Amino Acid Sequence↗
PubMed1982

Neuronal substance P in the esophagus. Distribution and effects on motor activity.

Substance P-immunoreactive nerve fibres were fairly numerous in the lower esophagus of the guinea-pig and cat but few in the pig. They were particularly numerous in the myenteric and submucosal plexuses but could be detected also in the circular and longitudinal smooth muscle and in the muscularis mucosae. Only in the cat were SP-immunoreactive cell bodies detected, albeit in low number, in the myenteric plexus. Radioimmunoassay showed that the lower part of the cat esophagus contained approximately 10 times more immunoreactive SP than the upper part and that the muscle layer contained more SP than the mucosa. Motor effects of synthetic SP were studied on segments from circular smooth muscle of cat esophagus. SP contracted the smooth muscle and enhanced the response to electrical stimulation. These effects of SP could be blocked by the specific SP antagonist (D-Pro2, D-Trp7, 9)-SP. The contractile response to electrical stimulation could be blocked by the cholinergic muscarinic blocker atropine and the opiate receptor agonist leu-enkephalin but not by the SP antagonist or by adrenergic blockers. Hence, the results suggest that cholinergic neurons innervate the circular smooth muscle, and that opiate receptor agonists suppress transmission in these neurons. Neuronal SP in the esophagus may serve to enhance the contractile responses of esophageal smooth muscle.

Animals↗
PubMed1981

Immunoreactive substance P in the chicken gut: distribution, development and possible functional significance.

The distribution and cellular localization of substance P in the chicken gut was studied by immunocytochemistry and immunochemistry. Substance P-containing nerve fibers are numerous in the gut wall. They occur in the smooth muscle layer as well as in the mucosa, where they are associated with blood vessels or surround the intestinal crypts. The fibers are particularly numerous in the myenteric and submucosal plexuses, where substance P-containing nerve-cell perikarya are also encountered. Substance P was found also in scattered endocrine cells of the small intestine, caeca and colon. Previously, bombesin-containing cells, which are numerous in the proventriculus, have been mistakenly identified as substance P cells due to cross-reactivity of certain antisera against substance P. Immunochemistry revealed the highest concentration of substance P differs slightly from that of synthetic bovine substance P, suggesting that chicken substance P differs structurally from mammalian substance P. Substance P-containing nerve fibers in the chicken gut develop slowly after hatching, apparently beginning in the duodenum; at approximately 20 weeks after hatching the distribution pattern is fully developed. A functional investigation was performed on the isolated chicken caecum to clarify the role of substance P in the contractile behavior of smooth muscle. Substance P contracted the caecum over a wide dose range; the contractile response was greater in 20 week-old chickens than in 4 and 10 week-old animals. Electrical field stimulation caused a relaxation of the caecum and a contraction upon cessation of stimulation. Neither of these responses, both of which are neurally mediated, were inhibited by adrenergic and cholinergic blockade. It is conceivable that the contractile response following electrical stimulation is caused by substance P released from nerve fibers in the smooth muscle.

Animals↗
PubMed1981

Peptide-containing neurons intrinsic to the gut wall. An experimental study in the pig.

Nerve fibers containing substance P, VIP, enkephalin or somatostatin are numerous in the porcine gut wall. They are particularly numerous in the submucosal and myenteric plexuses where peptide-containing cell bodies are also observed. Peptide-containing nerve fibers occur also in the vagus nerves, suggesting that the gut receives and extrinsic supply of peptidergic nerves. The extrinsic contribution to the peptide-containing nerve supply of the gut wall has not yet been quantitatively assessed. In an attempt to clarify this question pigs were subjected to bilateral subdiaphragmatic vagotomy. Another group of animals was subjected to complete extrinsic denervation by autotransplantation of a jejunal segment. The pigs were killed at various time intervals after the operations; the longest time interval studied was four months. Following vagotomy the innervation pattern of the jejunum appeared completely unaffected. Following complete extrinsic denervation the adrenergic nerve fibers disappeared, while peptide-containing and acetylcholinesterase-positive nerve fibers remained apparently unaltered. This was confirmed chemically in the case of substance P. The motor activity of smooth muscle from the jejunum was studied in vitro. At low stimulation frequencies the smooth muscle from control jejunum responded by relaxation; upon cessation of stimulation a contraction occurred. With increasing stimulation frequencies the duration of the relaxation decreased; at high frequency stimulation only a contraction was recorded. In the autotransplant low frequency stimulation induced no or only a weak relaxation; high frequency stimulation induced contraction. After cholinergic and adrenergic blockade, the muscle responded with relaxation at all frequencies; the response was similar in innervated and denervated specimens. On the whole, the effects of extrinsic denervation on the motor activity of smooth muscle from porcine jejunum were minor, possibly reflecting the high degree of autonomy of the gut.

Animals↗
PubMed1981

Tissue concentration and release of substance P-like immunoreactivity in the dental pulp.

The concentration of substance P-like immunoreactivity (SPLI) was determined in dental pulps from cat, dog and man by radioimmunoassay. Pulps from mature cats showed the highest SPLI-levels (mean 32 pmol/g); these are comparable to or higher than those found in any other organ outside the central nervous system. The SPLI concentrations were lower in pulp from immature teeth. The immunological and chromatographic behaviour of the pulpal SPLI from cat and man resembled that of synthetic substance P (SP), indicating that the assayed substance is closely related to or identical with SP. Release of pulpal SPLI in canine teeth was evoked by stimulation of the inferior alveolar nerve in anaesthetized cats. In 9 of 16 experiments the amounts of SPLI found in pulp suprafusates following stimulation (4-31 fmol) were larger than those in unstimulated controls (0-7 fmol). Stimulation also reduced the pulpal tissue concentration of SPLI to 60% of that in homologous control pulps. The high concentration of SPLI found in the dental pulp and the demonstration of nerve-induced release strengthen the hypothesis that SP serves some function in the dental pulp.

Adolescent↗
PubMed1981

Depletion of substance P-like immunoreactivity in the cat dental pulp by antidromic nerve stimulation.

Tissue levels of substance P-like immunoreactivity (SPLI) were determined by radioimmunoassay in incubated cat dental pulps with and without previous electrical stimulation of the inferior alveolar nerve (I.A.N.). The ability of the dental pulp to degrade substance P (SP) was also studied. The pulpal SPLI levels in teeth incubated at 37 degrees C for up to 240 min immediately after removal from the jaws did not differ from those in contralateral unincubated teeth. Following I.A.N. stimulation (3-45 min at 10 V, 15 Hz and 5 ms) and subsequent incubation (30 min at 37 degrees C) of the teeth the SPLI levels in ipsilateral pulps were significantly lower (45% reduction) than those in contralateral unstimulated controls. Incubation of homogenized pulp tissue at 37 degrees C with synthetic bovine SP or 125I-Tyr8-SP led to rapid inactivation of SP, whereas similar incubation of whole blood with 125I-Tyr8-SP had little effect. Endogenous SPLI levels were also rapidly reduced (50% reduction within 3 min) in incubated pulp homogenates. Incubation at a lower temperature (22 degrees C) resulted in a somewhat reduced rate of degradation and incubation with boiled homogenates failed to inactivate SP. The results indicate that the pulp contains enzymes capable of destroying SP and that within the nerve terminals SP is stored in such a way that it is protected against degradation. The data obtained also provide further evidence for a nerve evoked release of SP.

Animals↗
PubMed1981

Concentration of substance P-like immunoreactivity (SPLI) in tissues of dog, rat and mouse.

The distribution of SPLI in various tissues from dog, rat and mouse was determined by radioimmunoassay. The gastrointestinal, urogenital and tracheobronchial tracts were found to contain SPLI with marked differences in levels in different parts of these tracts. Glandular tissues, such as salivary glands and pancreas, was well as eye, tongue and skin also contain SPLI. Species differences were encountered both in absolute amounts and the distribution of SPLI. The highest concentrations of SPLI were generally found in mouse followed by dog and rat. The present results are in agreement with those of previous studies in which SP was demonstrated by bioassay technique, but due to the greater sensitivity of the radioimmunoassay it was possible to show a much wider distribution of SP. Virtually all organs in which an effect of SP has been demonstrated also contain SPLI.

Animals↗
PubMed1981

Evidence that substance P is a mediator of antidromic vasodilatation using somatostatin as a release inhibitor.

The effect of somatostatin on nerve-induced vasodilatation and the release of substance P (SP) was studied in the dental pulp of anesthetized cats. Changes in pulpal blood flow were determined by measuring the rate of disappearance of a local depot of radioactive tracer. The release of SP was studied indirectly by determining the residual amounts of substance P-like immunoreactivity (SPLI) in the pulps by radioimmunoassay. Electrical stimulation (3 min at 10 V, 15 Hz and 5 ms) of the distal end of the cut inferior alveolar nerve (IAN) increased pulpal blood flow. After pretreatment (10 min) with somatostatin (30 pmol/min) similar nerve stimulation was without effect on pulpal blood flow. Intra-arterial infusion of somatostatin (30 pmol/min) had no effect on pulpal blood flow and did not influence the vasodilator response to SP. Following IAN stimulation (3--45 min) and subsequent incubation (30 min, 37 degrees C) of the lower canine teeth, the SPLI levels in ipsilateral pulps were significantly lower (47.5% reduction) than those in contralateral, unstimulated controls. In cats pretreated with somatostatin (30 pmol/min for 10 min, i.a.) similar nerve stimulation (3 min) did not reduce the pulpal SPLI levels as compared to controls. The results show that nerve-induced vasodilatation and release of SPLI are inhibited by somatostatin. They are consistent with the hypothesis that vasodilatation in the cat dental pulp produced by stimulation of the IAN is mediated by substance P.

Alveolar Process↗
PubMed1980

Axonal transport of substance P in the vagus and sciatic nerves of the guinea pig.

The axonal transport and apparent subcellular distribution of substance P-like immunoreactive material (SPLI) were examined in nerves of guinea pigs by means of a sensitive radioimmunoassay and by immunohistofluorescence. Crushes or ligations were made at various levels above and below the nodose ganglion of the vagus, on the sciatic nerve, and on the central process of the S1 spinal ganglion. From the relative rates of accumulation of SPLI in the adjacent segments, it was concluded that the bulk of the substance P produced in the sensory ganglion cells was being exported toward the terminal regions of their peripheral branches. The average velocity of transport of SPLI in the peripheral direction was calculated to be 1 mm/h in the sciatic nerve and 1.25 mm/h in the vagus. The removal of SPLI from regions of nerve distal to a ligature indicated that only 26% of the peptide in vagus nerve and 17% of the peptide in sciatic nerve was available for rapid transport. It was therefore estimated that the mean velocity of the moving fraction was 5-6 mm/h. Stop-flow experiments with local cooling and rewarming in vivo suggested that some SPLI may have been transported as rapidly as 10 mm/h. The behavior of SPLI during ultracentrifugation of nerve and ganglion extracts indicated that this peptide was normally present both in a soluble form and in association with particles but was transported primarily in the latter form.

Animals↗
PubMed1980

Interaction of substance P with dispersed pancreatic acinar cells from the guinea pig. Binding of radioiodinated peptide.

Tyr8-SP has been radioactively labeled with 125I to a specific activity of 200 microCI/microgram. This tracer has been found to be rapidly and reversibly bound in a specific way to dispersed pancreatic acinar cells. The specific binding is saturable and dependent on incubation temperature. At 37 degrees C 125I-tyr8-SP is bound to a less degree than at lower temperatures since the peptide is rapidly degraded at 37 degrees C. Native SP inhibits binding of tracer. Results have been analyzed according to Scatchard and suggest 2 functionally distinct types of binding sites; a small number of sites with high affinity and a larger number of sites with low affinity for SP. SP-sites also bind eledoisin and physalaemin which are peptides similar to SP in terms of chemical structure and biological activities. The concentration range in which SP, physalaemin, nd eledoisin inhibit binding of 125I-tyr8-SP correlates well with the range in which these peptides stimulate biochemical processes like outflux of 45Ca, accumulation of cyclic GMP and release of amylase from acinar cells.

Animals↗
PubMed1979

Effect of oral administration of calcium carbonate, Camalox and Novalucol on plasma gastrin concentration in duodenal ulcer patients.

In 6 patients having duodenal ulcer disease plasma gastrin concentrations were determined before and after the oral administration of 0.5--2 g of calcium carbonate, 2--4 tablets of Camalox and 2 tablets of Novalucol. No significant influence on basal plasma gastrin levels was noted indicating that antacids, whether they contain calcium carbonate or not, do not influence the basal plasma concentration of gastrin at occasional administration.

Administration, Oral↗