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

An in vivo model for the simultaneous study of the motility of the gallbladder, sphincter of Oddi and duodenal wall in the anesthetized cat was developed. Changes in gallbladder volume were recorded as well as changes in the outflow from the sphincter of Oddi and from a vein graft inserted through the duodenal wall during perfusion at constant pressure. The distribution of three peptide hormones (substance P-SP, vasoactive intestinal peptide-VIP and cholecystokinin-CCK) within the feline extrahepatic biliary tree was studied immunocytochemically. Nerve terminals with SP-like immunoreactivity (LI) were distributed to the smooth muscle layers and also to acetylcholinesterase-positive ganglions cells in the intrinsic plexa. SP-LI was further demonstrated in cell bodies of the intrinsic plexa as well as in vagal axons. VIP-LI had a similar distribution. An especially rich VIP-ergic innervation was observed within the circular muscle layer of the sphincter of Oddi. SP-LI or VIP-LI did not occur in mucosal endocrine cells. On the other hand, CCK-LI was not demonstrated in nerves but occurred regularly in endocrine cells of the duodenal mucosa. Regional administration of SP elicited dose-dependent contractile motor effects on the biliary tree, which were not dependent on muscarinic or nicotinic cholinoceptors, but were inhibited by infusion of an antagonistic SP analogue indicating a direct effect on the smooth muscle cell. Efferent electrical vagal nerve stimulation elicited contractile motor responses, which were blocked by either atropine or infusion of the SP-analogue, indicating activation of a postganglionic cholinergic neuron via intrinsic or extrinsic SP neurons. These observation correlate well with the presence of SP nerve terminals on acetylcholinesterase-positive ganglion cells of the intrinsic plexa and SP axons within the vagus. An afferent mechanism cannot be excluded; antidromic activation of SP-containing axon collaterals from vagal afferents might act on intrinsic cholinergic neurons. The cellbodies of such afferents may be present in intrinsic plexa or within the sensory vagal nodose ganglion. VIP elicited relaxatory motor responses from the extrahepatic biliary tree, not influenced by blockade of cholinoceptors or beta-adrenoceptors. Stimulation of beta-adrenoceptors, or selective stimulation of beta 2-adrenoceptors caused dose-dependent relaxatory motor responses, which were antagonized by specific blockade. Stimulation of beta-adrenoceptors following selective blockade of beta 2-adrenoceptors resulted in relaxation, most probably mediated by beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The vagal nerves and peptides in the control of extrahepatic biliary motility. An experimental study in the cat. 170 May 77

Our study using feline tracheal isolated submucosal gland preparation has revealed that substance P (SP) produces an increase in submucosal gland secretion through the actions of both mucus ejection by glandular contraction and macromolecule secretion from secretory cells, and that the two actions are both mediated by a peripheral cholinergic action. In contrast, SP has no significant effect on macromolecule secretion from secretory cells in tracheal explants, probably because of epithelial suppression. Our study using an isolated gland preparation has also indicated that VIP potentiates mucous glycoprotein secretion induced by cholinergic stimulation through an interaction between muscarinic and VIP receptors in secretory cells. However, VIP failed to induce any significant glandular contraction or relaxation, indicating a lack of VIP receptors or a difference in the subtypes of muscarinic receptors in myoepithelial cells in submucosa glands.
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PMID:Neuropeptides and airway submucosal gland secretion. 170 51

The possible trophic influence of the capsaicin-sensitive extrinsic innervation of the gastrointestinal mucosa was investigated. Rats were treated neonatally with capsaicin. The gastrointestinal content of serotonin and glucagon-like immunoreactivity were used as a measure of the effect on the endocrine gut mucosa and gastrointestinal aminopeptidase and alkaline phosphatase activities were used as a measure of the effect on the gut brush-border. The gastrointestinal content of the neuropeptides substance P, VIP and CGRP were used to monitor effects on the innervation of the gut. The depletion of substance P-immunoreactivity(-IR) and calcitonin gene-related peptide(CGRP)-IR in extracts of urinary bladder and lung from the capsaicin-treated rats is evidence of the efficacy of capsaicin treatment in affecting a loss of C-fibre sensory nerves. The significant depletion of CGRP-IR measured in the stomach and duodenum of capsaicin-treated rats indicated the loss of the C-fibre sensory innervation to the gastrointestinal tract. The gastrointestinal content of VIP and substance P, which are predominantly within intrinsic gut neurones, were unaffected by capsaicin treatment. In all regions of the gastrointestinal tract of capsaicin-treated rats, the serotonin and glucagon-IR levels were not significantly different from those in controls. Similarly the levels of activity of the brush-border enzymes were not significantly effected by capsaicin treatment. This suggest the absence of any major trophic influence of capsaicin-sensitive sensory nerves on the gut endocrine mucosa and the brush border.
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PMID:Regulatory peptide and serotonin content and brush-border enzyme activity in the rat gastrointestinal tract following neonatal treatment with capsaicin; lack of effect on epithelial markers. 170 47

Immunohistochemical localization of substance P (SP), CGRP, VIP, neuropeptide Y (NPY), and somatostatin (SOM) in the carotid labyrinth were compared in some species of amphibians using the peroxidase-antiperoxidase method. Immunoreactivity of SP, CGRP, VIP, and NPY was found in the nerve fibers distributed in the intervascular stroma of the carotid labyrinth. SP, CGRP, and VIP immunoreactive varicose fibers were densely distributed in the peripheral portion of the carotid labyrinth. Some SP-immunoreactive fibers were distributed similarly to CGRP-immunoreactive fibers. The density of NPY and SOM immunoreactive varicose fibers was low. No immunoreactivity of enkephalins was observed in the labyrinth. The intensities of these peptides were varied from species to species. No glomus cells showed immunoreactivity for any of the 7 peptides studied. These results suggest that the vascular regulatory function, which is one of the possible functions of the carotid labyrinth, is controlled by the peptidergic mechanisms in addition to regulation through intimate apposition of glomus and smooth muscle cells (g-s connection).
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PMID:Localization of substance P, CGRP, VIP, neuropeptide Y, and somatostatin immunoreactive nerve fibers in the carotid labyrinths of some amphibian species. 171 15

1. Mechanical activity was recorded in isolated muscle preparations from circular and longitudinal layers of gastric fundus, corpus and antrum and from the duodenum of pigs, using conventional organ bath technique. Rectangular current pulses were applied to the muscle strips for electrical field stimulation (EFS). 2. Fundic and circular corpus preparations developed a marked spontaneous tonic activity. Vasoactive intestinal polypeptide (VIP, 10(-9)-10(-7) mol l-1) inhibited this spontaneous activity. This inhibitory effect was not affected by application of tetrodotoxin (TTX) showing its myogenic nature. 3. Pretreatment of fundic and circular corpus preparations with VIP reduced the excitatory responses to substance P, bombesin, serotonin and histamine, but it had no effect on the acetylcholine (ACh)-induced tonic and phasic activity. 4. Longitudinal duodenal preparations showed purely phasic activity which was almost insensitive to VIP. In circular duodenal preparations particularly strong spontaneous tonic contractions were observed which could be inhibited by VIP. 5. Circular duodenal preparations excised 3-5 cm postpyloric had a spontaneous tone which could reach up to 80% of the maximum contractions induced by 10(-4) mol l-1 ACh. These preparations were chosen for further pharmacological studies and for experiments with EFS. VIP was the most powerful substance for the inhibition of spontaneous tone, followed by serotonin, PGE2 and bradykinin. This type of preparation exhibited particularly strong inhibitory effects to EFS; even single stimuli could induce near maximum relaxation. The inhibition induced by EFS was unaffected by treatment with ATP, guanethidine, atropine, methysergide and apamin. TTX completely abolished the EFS-induced relaxation, showing its neurogenic nature. 6. Porcine circular duodenum is a good model for studying the transmitter system of the non-adrenergic, non-cholinergic (NANC) innervation. The results are consistent with the assumption that VIP is the transmitter in this system, although the very slow time-course of the VIP-induced inhibition in comparison with the EFS-induced inhibition is not consistent with this notion.
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PMID:Responses of porcine gastric and duodenal smooth muscle to VIP. 172 15

Human blood polymorphonuclear neutrophils (PMN) are thought to be involved in the pathogenesis of asthma through their recruitment into the bronchoalveolar lumen and the lung by local release of chemotactic factors. Therefore chemotactic activities of several mediators (PAF, histamine and three neuropeptides substance P, VIP and a somatostatin analog) were compared on blood PMN from both healthy subjects (HS) and asthmatic patients (AP). The maximal response to PAF was significantly different (P less than 0.05) with cells from both groups. Moreover activity for the HS peaked at 10(-6) M, whereas the AP showed peak chemotactic activity at 10(-8) M. Histamine had no chemoattractant effect on PMN. Substance P did not induce PMN locomotion, whereas VIP induced a chemotactic response in a dose-dependent manner, particularly with cells from HS as compared to those from AP. BIM 23014 (a somatostatin analog) exhibited chemotactic activity which was also more pronounced with PMN from HS as compared to those from AP. Our findings showed that blood PMN could be involved in asthma through their heightened locomotor reactions to mediators which are known to be released locally by activated cells in bronchoalveolar lumen.
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PMID:Neutrophil chemotactic activity of PAF, histamine and neuromediators in bronchial asthma. 172 27

By immunocytochemistry, substance P immunoreactive (SP-IR) and vasoactive intestinal peptide immunoreactive (VIP-IR) nerve fibers were examined in guinea pig mesenteric lymph collectors. The immunoreactive nerve fibers, located in the adventitia of lymphatics, were few and were irregularly distributed along the vessel wall. These fibers appeared to be more numerous and more evenly distributed along the corresponding artery and vein walls within the same area. SP immunoreactivity in the vascular nerves was depleted in guinea pigs injected with capsaicin but was unaffected by the injection of 6-hydroxydopamine. By contrast, VIP-IR nerve fibers were unaffected by both treatments. It is concluded that SP-IR nerve fibers in the lymphatics are likely to be of sensory origin and that VIP containing nerves in the lymph collectors are distinct from SP-containing and noradrenergic nerves. It is also suggested that lymph collectors possess a complex although limited innervation pattern not only of autonomic nerve fibers containing classic neurotransmitters but also of peptidergic nerve fibers of a different origin with a vasomotor and/or sensory action.
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PMID:Peptidergic innervation of mesenteric lymphatics in guinea pigs: an immunocytochemical and pharmacological study. 172 75

Plasma levels of the neuropeptides, vasoactive intestinal polypeptide (VIP, neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P, and galanin were determined in 15 hyperthyroid patients before and at 3 occassions during 38 weeks of treatment. Treatment was performed with either 131I alone or with carbimazole, with combination of carbimazole and thyroxine, or with subtotal thyroidectomy. Before and after 11 (+/- 4), 24 (+/- 6) and 38 (+/- 5) weeks of treatment, plasma neuropeptide levels were analysed. A group of 9 premenopausal women served as controls. During hyperthyroidism, mean plasma level of CGRP was higher than in controls (P less than 0.001). In contrast, the mean plasma levels of the other measured neuropeptides did not differ from those in the controls. Mean serum level of tree T4 was lowered from 81.9 +/- 30.1 to 23.9 +/- 8.6 pmol/l and mean serum level of free T3 was lowered from 27.3 +/- 7.9 to 6.7 +/- 2.3 pmol/l during the course of the treatment. After 11 weeks of treatment, mean plasma NPY level was significantly increased (P = 0.004) compared to pretreatment levels. However, after 38 weeks of treatment, mean plasma NPY level had returned to control values. The mean plasma CGRP level was significantly reduced at 11 and 38 weeks of treatment compared to pre-treatment value (P = 0.002 and P = 0.004, respectively). Mean plasma level of neurotensin slowly declined during the treatment (P = 0.003). In contrast, mean plasma level of VIP, of substance P, and of galanin did not differ from control value before or after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma neuropeptides in hyperthyroidism. 172 11

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.
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PMID:Molecular anatomy of the neuro-immune connection. 177 30

Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome.
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PMID:Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity. 194 36


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