Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In longitudinal muscle strips of rat forestomach, metoclopramide (Mcp) increased the height of cholinergic-mediated contractions evoked by electrical field stimulation, probably by facilitating the release of neuronal acetylcholine. This response to Mcp was not prevented by drugs which blocked the synthesis of prostanoids or the actions of nicotine, morphine, noradrenaline, histamine and substance P. An involvement of dopamine in the mechanism of the response to Mcp was also excluded. Tachyphylaxis with 5-hydroxytryptamine (5HT) increased the electrically-evoked contractions and prevented the response to Mcp. Of the 5HT antagonists tested, only high concentrations of methysergide or phenylbiguanide reduced the ability of Mcp to increase the cholinergic-mediated contractions. These experiments are discussed in relation to the possibility that Mcp may increase neuronal ACh release in the gut by affecting 5HT synthesis or by acting on 5HT receptors.
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PMID:The effects of various pharmacological agents on the metoclopramide-induced increase in cholinergic-mediated contractions of rat isolated forestomach. 241 53

Rats with streptozotocin-induced diabetes of 10 weeks' duration showed significant changes in the total content of somatostatin, substance P and vasoactive intestinal polypeptide in the stomach and small intestine compared with control animals. An increase (p less than 0.05) in the concentration and total content of gastric somatostatin and a decrease (p less than 0.05) in the concentration and content of gastric substance P were seen in the streptozotocin-treated rats. The increase in the vasoactive intestinal polypeptide (VIP) content (54%, p less than 0.05) and the decrease in the substance P content (35%, p less than 0.05) of the gut may contribute to the impaired intestinal motility observed in animals with experimentally produced diabetes. Both the diabetogenic effect of streptozotocin and the changes in regulatory peptide concentrations were prevented by injection of nicotinamide before streptozotocin suggesting that the changes did not arise from a non-specific toxic effect of streptozotocin upon gastrointestinal neurones and/or endocrine cells.
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PMID:Changes in the somatostatin, substance P and vasoactive intestinal polypeptide content of the gastrointestinal tract following streptozotocin-induced diabetes in the rat. 241 23

The distribution of vasoactive intestinal polypeptide (VIP) and substance P-like immunoreactivities was studied by immunohistochemistry in the myenteric plexus and circular muscle layer of the ileum and proximal colon of rats 8 wk after induction of diabetes with streptozotocin. A consistent increase was observed in fluorescence intensity of VIP-like immunoreactivity in the nerve fibers, and intensely stained cell bodies were significantly more frequent in the myenteric plexus of the ileum (p less than 0.001) from diabetic animals. Some varicosities of VIP-like immunoreactive fibers in the myenteric plexus appeared to be enlarged. Vasoactive intestinal polypeptide-like immunoreactivity was increased and VIP-like immunoreactive nerves appeared thicker in the circular muscle layer of both diabetic ileum and proximal colon. The VIP levels were measured biochemically in tissue consisting of the smooth muscle layers and myenteric plexus. A significant increase in the VIP content per centimeter of intestine was found in both the ileum (p less than and proximal colon (p less than 0.01) from diabetic rats. In contrast, no apparent change in substance P innervation was observed immunohistochemically in the myenteric plexus and circular muscle layer of either diabetic ileum or proximal colon when compared with controls. The results are discussed in relation to the symptoms of autonomic neuropathy of the gut in diabetes.
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PMID:Enteric nerves in diabetic rats: increase in vasoactive intestinal polypeptide but not substance P. 241 33

The effect of efferent electrical stimulation of the divided thoracic vagus nerves on the release of substance P-like immunoreactivity (SPLI) into the portal vein was studied in anesthetized cats. Under basal conditions portal SPLI levels were fairly constant. During the first 5 min of vagal stimulation there was a significant increase of the portal plasma levels of SPLI. Since we have demonstrated that infracardiac vagal stimulation causes only minor changes in small intestinal bloodflow, a true vagal neurogenic release of SPLI seems likely. We have shown that SPLI is exclusively localized within feline gut neurons (not the enterochromaffin (EC) cells). Thus, SPLI released into the portal circulation probably represents overflow of transmitter into the circulation. Neither blockade of cholino- or adrenoceptors nor ganglionic blockade influenced the enhanced release of SPLI induced by vagal stimulation, suggesting activation of SP neurons via nonclassical receptors.
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PMID:The influence of cholinergic and adrenergic blockade on the portal release of substance P in the cat. 241 79

Metabolites of substance P, produced by incubation with isolated epithelial cells and with purified brush border and basolateral membrane from pig small intestine, were isolated by high performance liquid chromatography and identified by amino acid analysis. Rapid cleavages between Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10 and oxidation of the methionine residue at position 11 were observed with cells and with both membrane fractions. Formation of substance P3-11' indicative of the action of dipeptidylaminopeptidase IV (EC 3.4.14.5), was observed only at high substrate concentration. Proteolytic degradation was inhibited by phosphoramidon and by EDTA but was insensitive to chloride ion concentration and to captopril. These observations suggest that inactivation of substance P in the epithelial layer of the gut is mediated through endopeptidase-24.11 (EC 3.4.24.11) in the cell-surface membrane and that degradation by angiotensin-converting enzyme (EC 3.4.15.1), although present in high concentration in the mucosa, is unimportant.
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PMID:Proteolytic inactivation of substance P in the epithelial layer of the intestine. 241 32

This study reports on a difference in the inhibitory action of the neuropeptides somatostatin and Met-enkephalin on acetylcholine (ACh) release from myenteric plexus-longitudinal muscle strips of guinea pig small intestine. Met-enkephalin (8.7 X 10(-8) M) inhibited ACh release evoked by either substance P (3.7 X 10(-8) M) or neurotensin (7.5 X 10(-11) M), and this inhibition could be reversed by naloxone (5 X 10(-8) to 5 X 10(-5) M). Neurotensin-induced ACh release was also sensitive to the inhibition by somatostatin. However, when tested in a dose range from 6.1 X 10(-8) to 6.1 X 10(-6) M, somatostatin was ineffective in reducing the efflux of ACh evoked by substance P. These observations provided evidence to support the view that inhibitory peptidergic neurons within the myenteric plexus modulate the activity of cholinergic neurons with a high degree of specificity and that both somatostatin and Met-enkephalin have distinct neuromodulatory functions in the gut.
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PMID:Inhibitory peptidergic neurons: functional difference between somatostatin and enkephalin in myenteric plexus. 241 98

Vagal nerve stimulation caused a release of substance P (SP) and serotonin (5-HT) into the feline portal circulation. Both substances are gut spasmogens and were demonstrated in gut nerves by immunocytochemistry. In anesthetized cats gastric and pyloric motility were studied simultaneously at stimulation with SP or 5-HT via the splenic artery or at stimulation of the extrinsic nerves to evaluate their role in the motor control of these regions. The vagally induced pyloric contraction was noncholinergic and nonadrenergic but sensitive to hexamethonium in contrast to the cholinergic gastric contraction, which was resistant to ganglionic blockade. Splanchnic nerve stimulation caused relaxatory gastropyloric responses; the gastric relaxation was sensitive to adrenergic or ganglionic blockade in contrast to the pyloric relaxation. Infrequent contractile responses were seen, which were antagonized by atropine. Injection of SP via the splenic artery elicited contractile gastropyloric responses, which were sensitive to atropine and an antagonistic SP-analogue (SPA) but resistant to hexamethonium, indicating SP activating a final cholinergic neuron. The vagally induced pyloric contraction was resistant to atropine but sensitive to SPA and hexamethonium, indicating involvement of SP in the activation of preganglionic neurons as well. Involvement of SP in a vagal afferent mechanism is possible, since heat activation of the distal end of the divided vagal nerve induced a gastric contraction, sensitive to atropine and SPA but not to ganglionic blockade, indicating antidromic activation of SP afferents which via axon collaterals excite cholinergic neurons. A regional difference between stomach and pylorus was suggested by the different motor responses after pharmacological blockade, heat-activation or i.a. injection of capsaicin. The contractile pyloric responses to 5-HT were antagonized by peripheral blockade of 5-HT2 receptors. However, such blockade did not influence the motor responses to extrinsic nerve stimulation, suggesting that 5-HT is not essential for the mediation of these responses. The contractile responses to SP or 5-HT were studied in vitro in antral and pyloric strips from the rat. These responses were antagonized by SPA or SP tachyphylaxis and peripheral blockade of 5-HT2 receptors respectively. The responses were not reduced by tetrodotoxin, indicating main activation of muscular receptors. However, the contractile responses were reduced by atropine or hexamethonium, except the SP-induced pyloric contraction, which was atropine-sensitive but hexamethonium-resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the role of substance P and serotonin in the pyloric motor control. An experimental study in cat and rat. 241 34

To determine if chemicals produced endogenously within the gastrointestinal system stimulate abdominal visceral sensory endings, we recorded the response of 42 A- and 25 C-fibers in the splanchnic nerve of cats as substance P (10-20 micrograms), 5-hydroxytryptamine (5-HT, 100-200 micrograms), or bradykinin (10 micrograms) was injected into the descending thoracic aorta. Approximately half of the sensory endings responded to each chemical. However, significantly more C- than A-fiber endings responded to 5-HT (64 vs. 39%) and bradykinin (76 vs. 41%). Most C-fiber endings were insensitive to external mechanical stimuli, supporting the concept that these endings are primarily chemosensitive. In contrast, most A-fiber endings were quite sensitive to external mechanical stimuli. Additionally, more A-fiber endings located in contractile (gut or vasculature) than in noncontractile (pancreas, liver, or spleen) regions responded to 5-HT (58 vs. 19%), bradykinin (67 vs. 15%), and substance P (57 vs. 29%), a response that frequently occurred coincident with the development of chemically induced gut contractions. Thus many A-fiber endings are primarily sensitive to mechanical stimuli. However, 15-30% of the A-fiber endings located in noncontractile regions responded to chemicals, although the endings likely were removed from the mechanical effects of these chemicals. Since these A-fiber endings are also quite sensitive to external mechanical stimuli, they may be polymodal in their function. We conclude that abdominal visceral sensory endings are not homogeneous in function and are stimulated by several chemicals produced endogenously within the gastrointestinal system, including substance P, 5-HT, and bradykinin.
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PMID:Substance P, 5-hydroxytryptamine, and bradykinin stimulate abdominal visceral afferents. 2420 60

A monoclonal antibody against substance P was used for immunocytochemical staining of the central ganglia of the snail Helix aspersa and several peripheral tissues including the gut, reproductive system, cardiovascular system, tentacle and other muscles. Within the central ganglia many neurons, and many fibres in the neuropile and the nerves entering the ganglia, were stained for the SP-like material. The largest numbers of reactive cell bodies were in the pleural ganglia and on the dorsal surfaces of the pedal ganglia. A group of cells was also found, surrounding the right pedal-cerebral connective, that did not fluoresce, but were enveloped by reactive processes terminating directly onto the neurone somata. Specific staining was observed in all peripheral tissues examined and always appeared to be concentrated in nerve terminals. Most particularly these occurred in the heart and aorta, the pharyngeal retractor muscle and the tentacle. Although mostly present in muscular tissues, some fluorescence was also observed in the nervous layer surrounding the retina. The tentacular ganglion also contained immunoreactive cell bodies.
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PMID:Localization of a substance P-like material in the central and peripheral nervous system of the snail Helix aspersa. 242 Jul 66

Human enteric innervation was studied immunochemically with neuron-specific-enolase (NSE), a specific neurone marker indicative of differentiation, and substance P, a potent member of the family of neuropeptides. By examining various levels of the gut in 28 normal human fetuses of gestational ages 9 to 21 weeks, we showed that enteric neurones as a whole, as well as peptidergic neurones in particular, followed a dual gradient of development proceeding from each end to the middle of the gut. This suggests the need for caution in accepting the hypothesis of the pathogenesis of Hirschsprung's disease based on the concept of a single craniocaudal gradient of enteric neuronal development. In studies of six infants with Hirschsprung's disease, NSE immunostaining was found to be potentially useful for diagnostic purposes. NSE activity suggested that the hypertrophied nerve bundles in aganglionic bowel were metabolically active and functionally mature. Substance P-immunoreactivity was decreased in both aganglionic and distal ganglionic bowel in Hirschsprung's disease, suggesting that substance P-nerves were more extensively affected developmentally than other enteric neurones. In 28 infants with pyloric stenosis (IHPS), the presence of intense NSE activity in the ganglia in the pylorus suggested that these neurones were neither immature nor severely degenerated. A decrease in substance P immunoreactivity in IHPS suggested possible involvement of peptidergic innervation in the pathogenesis of IHPS.
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PMID:An immunochemical study with neuron-specific-enolase and substance P of human enteric innervation--the normal developmental pattern and abnormal deviations in Hirschsprung's disease and pyloric stenosis. 242 Sep 55


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