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Biomedical subjects

A Saria

Publications and source records attributed to A Saria.

At least 181 records · Page 10Linked to original sources
PubMed1983

Capsaicin-induced substance P release and sensory control of vascular permeability in the guinea-pig ureter.

Substance P-immunoreactivity (SP-IR) in the guinea-pig ureter was found to be totally depleted after systemic capsaicin pretreatment. Removal of the inferior mesenteric ganglion (IMG) led to a total depletion of SP-IR from the rostral third of the ureter and to a partial depletion from the caudal third. Electrical stimulation of the IMG caused Evans blue extravasation mainly in the rostral third of both ureters, whereas stimulation of the right pelvic nerve caused Evans blue extravasation in the caudal third of the ureters on both sides. The responses to nerve stimulation were absent in capsaicin-pretreated animals. Furthermore, capsaicin caused release of SP-IR from ureter slices in vitro, this release was not inhibited by tetrodotoxin. Potassium (60 and 120 mM) also released SP-IR. It is concluded that SP-IR in the ureter is contained in capsaicin-sensitive sensory neurons reaching the ureter via both parasympathetic (caudal part) and sympathetic nerves (rostral part). Activation of these neurons by capsaicin leads to a peripheral release of SP-IR which most likely increases vascular permeability.

Animals↗
PubMed1983

Vascular protein linkage in various tissue induced by substance P, capsaicin, bradykinin, serotonin, histamine and by antigen challenge.

Plasma extravasation was induced in rats or guinea-pigs by intravenous injections of (1) substance P (SP), (2) the C-terminal SP-hexapeptide SP(6--11), (3) serotonin (5-HT), (4) histamine, (5) bradykinin, (6) capsaicin and (7) by antigen challenge. Plasma extravasation induced by SP, SP(6--11), by 5-HT and by capsaicin was, with few exceptions, observed in the same tissues. The effect of SP was not blocked by H1 and H2 histamine receptor antagonists. The effect of i.v. capsaicin was absent in capsaicin desensitized animals. Plasma extravasation upon i.v. SP, SP(6--11), 5-HT and capsaicin was seen in the skin and in all organs containing mucous membranes except the intestinal mucosa. Plasma extravasation by histamine, bradykinin, and antigen challenge of sensitized guinea-pig was, in addition, also observed in the stomach and intestine. Plasma extravasation and bronchoconstriction by antigen challenge with 20 micrograms/kg ovalbumin was completely blocked by combined H1 and H2 histamine receptor blockade. Both responses were reduced to about the half capsaicin desensitized guinea-pigs, although the reduction of the permeability response was statistically not significant in all organs. In conclusion, several substances including anaphylaxis induce protein leakage in many tissues with differing selective distribution patterns. Anaphylactic histamine release leads to protein leakage partly via activation of sensory neurons. SP is a likely mediator of neurogenic protein leakage in many organs.

Animals↗
PubMed1983

Release of histamine by neuropeptides from the perfused rat hindquarter.

The release of histamine and serotonin by neuropeptides and capsaicin was measured in the isolated perfused rat hindquarter preparation. Substance P and two antagonistic peptides, [D-Pro2, D-Phe7, D-Trp9]-SP and [D-Pro2, D-Trp7,9)]-SP, release histamine, the SP(4-11) and SP(6-11) analogues did not. VIP and somatostatin released histamine and also serotonin. No amines were released by bombesin. Thus, all amine releasing peptides possessed at least two basic charges. However, the histamine releasing activity of the neuropeptides tested did not correlate with their reported ability to cause vasodilation and plasma extravasation. The SP(4-11) and SP(6-11) analogues which did not release histamine caused plasma extravasation. It is concluded that SP causes plasma extravasation by a direct action on blood vessels. Capsaicin released only serotonin but no histamine either in untreated rats and such desensitized with capsaicin as neonates. In rats desensitized with capsaicin 4 days prior to the experiment the substance P induced histamine release was as high as in untreated controls; it was, however, absent in rats desensitized with capsaicin as neonates. It is assumed that the sensitivity of mast cells to substance P is lost after degeneration of substance P containing primary sensory fibers.

Animals↗
PubMed1983

Capsaicin pretreatment inhibits heat-induced oedema in the rat skin.

Exposure of rat paws to noxious heat (hot water, 48 degrees C) led to an increase in vascular permeability to macromolecules as indicated by extravasation of Evans blue dye. After pretreatment of neonatal rats with 50 mg X kg-1 capsaicin s.c., which is known to cause degeneration of unmyelinated afferent neurones, this protein leakage was reduced by 74% (P less than 0.01). It is concluded that the oedema induced by noxious heat is partially caused by excitation of peripheral endings of capsaicin-sensitive primary afferent neurones.

Animals↗
PubMed1983

Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues.

The dye Evans blue was used to monitor vascular protein leakage. Fluorometric measurement of Evans blue in formamide extracts of rat tracheal tissue was performed after induction of protein leakage by electrical vagus nerve stimulation and compared with the widely used colorimetric detection. The fluorescence method was approximately 100 X more sensitive than the colorimetric method. Furthermore, Evans blue fluorescence (excitation at 620 nm, emission at 680 nm) was used for microscopic investigation of cryostat sections of tracheal tissue. Extravasated Evans blue after electrical nerve stimulation was mainly found in the subepithelial layer of the trachea obviously bound to tissue constituents. It is suggested that Evans blue fluorescence can be applied for quantification of protein leakage with high sensitivity which opens the possibility of measuring this reaction in very small regions with high accuracy, as well as for tissue localization of protein leakage at the microscopic level.

Animals↗
PubMed1983

Cigarette smoke-induced airway oedema due to activation of capsaicin-sensitive vagal afferents and substance P release.

Exposure of rats to smoke from one cigarette caused local oedema due to a marked increased in vascular permeability from the epiglottis down to bronchioli, as indicated by extravasation of Evans blue in the airway mucosa. The cigarette smoke-induced extravasation of Evans blue was still present after removal of the tar and nicotine content of the smoke, suggesting that chemical irritants in the vapour phase were the main mediators of the vascular permeability response. Local or systemic pretreatment with capsaicin or [D-Arg1, D-Pro2, D-Trp7,9, Leu11] SP, a substance P antagonist, abolished or significantly reduced the airway oedema induced by cigarette smoke or vagal nerve stimulation. No reduction of the cigarette smoke or vagally induced tracheal oedema was seen upon pretreatment with mepyramine plus cimetidine, fentanyl, disodiumchromoglycate, methylprednisolone or terbutaline. The results thus indicate that the cigarette smoke or vagally induced tracheal oedema is most likely to be due to substance P release from local capsaicin-sensitive afferent neurons in the airway mucosa. Local administration of substance P antagonists may be considered as a pharmacological means of inhibiting local mucosal oedema in the airways caused by airway irritants such as cigarette smoke.

Afferent Pathways↗
PubMed1983

A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig.

Electrical stimulation of the cervical vagus nerve in anesthetized guinea pigs induced a rapid increase in respiratory insufflation pressure, suggesting increased airway resistance. After intravenous administration of a substance P (SP) antagonist, [D-Arg(1),D-Pro(2),D-Trp(7,9),Leu(11)]SP, the insufflation pressure response to vagal stimulation was reduced by 78% while the cardiovascular effects were unchanged. Histamine receptor-blocking agents were used to inhibit the effects of histamine release induced by the SP-antagonist. [D-Arg(1),D-Pro(2),D-Trp(7,9),Leu(11)]SP also reduced the increase in insufflation pressure caused by intravenous SP or capsaicin. The long-lasting noncholinergic contraction of the main and hilus bronchi induced by field stimulation in vitro, as well as the contractile effects of SP and capsaicin, were also blocked by the SP antagonist. The cholinergic contractions and the noncholinergic tracheal relaxation on field stimulation in vitro were, however, not blocked by the antagonist. Vagal stimulation in vivo also increased vascular permeability in the respiratory tract and esophagus, causing a subepithelial edema as indicated by Evans blue extravasation. Previous treatment with [D-Arg(1),D-Pro(2),D-Trp(7,9),Leu(11)]SP inhibited the permeability increase induced by both vagus nerve stimulation and exogenous SP. SP release from vagal sensory nerves was indirectly shown by reduction in the bronchial levels of SP after nerve stimulation in vivo. The data suggest that a major portion of the vagally or capsaicin-induced increase in smooth muscle tone is caused by SP release from sensory neurons. In addition, activation of vagal SP-containing sensory nerves induces local edema. Tracheobronchial afferent SP-containing C fibers may thus exert local control of smooth muscle tone and vascular permeability in normal and pathophysiological conditions.

Amino Acid Sequence↗
PubMed1983

Substance P and capsaicin-induced contraction of human bronchi.

Substance P induced a dose-dependent contraction of human segmental bronchi in vitro with a threshold dose of about 10(-6) M. These preparations were obtained from patients undergoing lung tumor surgery. The substance P-induced contractions were resistant to mepyramine and atropine, suggesting a direct effect on the bronchial smooth muscle. Capsaicin (10(-5) M) also induced a slowly developing strong atropine-resistant contraction of human bronchi in vitro. a rapid tachyphylaxis developed for the response to capsaicin. Both substance P and capsaicin were less potent than acetylcholine and histamine in inducing contractions of human bronchi. This finding may however be partly due to the experimental conditions and both substance P and capsaicin were comparatively much more potent in guinea-pig preparations. Transmural field stimulation of the bronchial preparations in man resulted in contractions that were largely sensitive to atropine. The presence of capsaicin-induced bronchial contractions however indicates the existence of a local non-cholinergic axon-reflex control of bronchial smooth muscle tone by substance P in man.

Acetylcholine↗
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↗
PubMed1982

A study of the concentrations of substance P and neurotensin in the gastrointestinal tract of various mammals.

Immunoreactive substance P and neurotensin in extracts of the digestive tract of man, cat, guinea-pig, pig, rabbit, and rat were measured by radioimmunoassay using antisera directed against the C-terminal portions of the two peptides. In all species except the cat, the concentrations of substance P were highest in the small intestine, intermediate in the large intestine and lowest in the stomach and oesophagus: the digestive tract of the cat displayed a rather even distribution of substance P. As observed in the ileum of guinea-pig, rabbit, and rat, the external muscle layer including the myenteric plexus contained 2-5 times higher concentrations of substance P than the whole ileal wall, whereas the substance P concentrations in the mucosa were only about one sixth of those in the whole wall. High performance liquid chromatography of extracts of human, feline and rabbit ileum showed that all the immunoreactive substance P eluted at the positions of substance P and substance P sulfoxide. The distribution of immunoreactive neurotensin along the digestive system of all six species was very similar. The highest concentrations of neurotensin were measured in the distal part of the small intestine, whereas the large intestine, stomach and oesophagus contained only low concentrations of neurotensin relative to the concentrations in the ileum. As examined in the ileum of guinea-pig, rabbit, and rat, the mucosa exhibited 2.5-4 times higher concentrations of neurotensin than the whole ileal wall, while the concentrations of neutrotensin in the external muscle layer including the myenteric plexus were only 4-20% of those in the whole wall. High performance liquid chromatography of the immunoreactive neurotensin extracted from the cat ileum yielded a single peak corresponding to neurotensin while the immunoreactive neurotensin extracted from the ileum of man and rabbit was eluted in two peaks, 55 and 72% of the recovered immunoreactivity, respectively, corresponding to neurotensin. These findings are in line with the proposed roles of substance P in the neural, and neurotensin in the endocrine, control and maintenance of gastrointestinal motility.

Animals↗
PubMed1981

Histamine in tissue: determination by high-performance liquid chromatography after condensation with o-phthaldialdehyde.

Histamine was determined by reversed-phase high-performance liquid chromatography in perchloric acid extracts after condensation with o-phthaldialdehyde. Fluorescence was monitored at 360 nm excitation and 450 nm emission wavelengths after elution with mixtures of 0.1 N acetic acid containing 0.1% pentanesulfonic acid and acetonitrile. The detection limit was 0.9 pmol of histamine. The histamine content was determined in rat whole brain, medulla oblongata, dorsal and ventral spinal cord, dorsal and ventral skin of the hind paw, stomach, ileum, rectum, lung and a hind-quarter perfusate, and compared to published data. The advantages of the described method over other methods are (A) rapid analysis in an automated system, (B) no selective extraction procedure is necessary, and (C) interfering substances are easily separated from the histamine fluorophore.

Animals↗
PubMed1981

Determination of capsaicin in tissues and separation of capsaicin analogues by high-performance liquid chromatography.

Capsaicin, the pungent principle of chili peppers, and six analogues were characterized by reversed-phase high-performance liquid chromatography using isocratic methanol--water mixtures and UV detection. A highly sensitive method for the quantitative determination of capsaicin in animal tissues and blood has been developed. Using a reversed-phase column and acetonitrile--water mixtures for elution, 3 ng of capsaicin could be measured by fluorimetric detection at an excitation wavelength of 270 nm and an emission wavelength of 330 nm. Acetone extraction of tissue resulted in a recovery of approximately 90%. Extraction and determination of capsaicin in rat brain, spinal cord, liver and blood after i.v. administration is given as an example.

Animals↗
PubMed1981

Release of histamine by substance P.

1. The basic peptide substance P causes histamine release from peritoneal mast cells of the rat in vitro whereas the closely related neutral peptides eledoisin and physalaemin do not. 2. Infusion of substance P (7.4 nmol min-1), but not of eledoisin (8.4 nmol min-1) or physalaemin (7.9 nmol min-1), into the rat hindquarter preparation caused a more than 4-fold increase of the histamine content in the venous outflow. The outflow of 5-HT remained unchanged under infusion of all three peptides. 3. No histamine depletion in the skin of the rat hind paw was observed following antidromic stimulation of the saphenous nerve or cutaneous application of mustard oil. Infusion of substance P (7.4 nmol min-1) caused a 47% depletion of histamine in the paw skin although only a small proportion of the infused substance P seemed to enter the tissue from the blood vessels. 4. The results further substantiate the view that substance P upon release from peripheral nerve endings induces release of histamine from cutaneous mast cells, a mechanism which contributes to neurogenic vasodilatation and plasma extravasation.

Animals↗