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)

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.
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PMID:Neuronal cholecystokinin, gastrin-releasing peptide, neurotensin, and beta-endorphin in the intestine of the guinea pig. Distribution and possible motor functions. 632 15

Bombesin-like and gastrin-releasing peptide (GRP)-like immunoreactivities were localized in nerves of the guinea-pig small intestine and celiac ganglion with the use of antibodies raised against the synthetic peptides. The anti-bombesin serum (preincubated to avoid cross reactivity with substance P) and the anti-GRP serum revealed the same population of neurons. Preincubation of the anti-bombesin serum with bombesin abolished the immunoreactivity in nerves while absorption of the anti-GRP serum with either bombesin or the 14-27 C-terminal of GRP only reduced the immunoreactivity. The immunoreactivity was abolished by incubation with GRP 1-27. Immunoreactive nerves were found in the myenteric plexus, circular muscle, submucous plexus and in the celiac ganglion. Faintly reactive nerve cell bodies were found in the myenteric ganglia (3.2% of all neurons) but not in submucous ganglia. After all ascending and descending pathways in the myenteric plexus had been cut, reactive terminals disappeared in the myenteric plexus, circular muscle (including the deep muscular plexus) and the submucous plexus on the anal side. After the mesenteric nerves were cut no changes were observed in the intestinal wall but the reactive fibres in celiac ganglia disappeared. It is deduced that GRP/bombesin-immunoreactive nerve cell bodies in myenteric ganglia project from the myenteric plexus to other myenteric ganglia situated further anally (average length 12 mm), anally to the circular muscle (average length 9 mm), anally to submucous ganglia (average length 13 mm) and external to the intestine to the celiac ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distribution and projections of neurons with immunoreactivity for both gastrin-releasing peptide and bombesin in the guinea-pig small intestine. 636 96

An increasing amount of evidence concerning the existence of non-adrenergic, non-cholinergic autonomous nerves has been presented during the past decade. These nerves contain different peptides which may act as neurotransmitters. The pathophysiology in Hirschsprung's disease is not yet fully explained. To throw further light upon it, the distribution and occurrence of different peptide-containing (peptidergic) nerves was studied. A semiquantitative immuno-histochemical method was used to assess the distribution and occurrence of nerves containing encephalin, GRP (gastrin-releasing peptide), VIP (vasoactive intestinal peptide) or substance P in four patients operated by Duhamel's procedure. The results indicate a total absence of encephalin and GRP containing nerves in the aganglionic segment. Such nerves could, however, be found in the normally ganglionated part of colon. The nerves containing VIP and substance P were fewer in the aganglionic segment than in the rest of the colon. The result is related to what is hitherto known about the specific effects of the different peptides.
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PMID:Peptidergic innervation in Hirschsprung's disease. 664 2

Guinea pig cochlear blood vessels were investigated with regard to their supply of adrenergic and peptidergic nerve fibers. Using the glyoxylic acid histofluorescence technique, numerous adrenergic fibers were seen around the labyrinthine artery, whereas the spiral modiolar artery contained only few such fibers. Immunocytochemistry revealed nerve fibers containing immunoreactive avian pancreatic polypeptide, vasoactive intestinal peptide, substance P, or gastrin-releasing peptide around the labyrinthine and spiral modiolar arteries. Adrenergic or peptidergic nerve fibers were not seen around the blood vessels of the stria vascularis. Upon removal of the superior cervical ganglion, adrenergic fibers disappeared and fibers displaying avian pancreatic polypeptide immunoreactivity were reduced in number. These data suggest co-occurrence of catecholamines and immunoreactive avian pancreatic polypeptide in a population of adrenergic nerves.
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PMID:Adrenergic and peptidergic innervation of cochlear blood vessels. 675 6

We labeled substance P (SP), neurokinin A (NKA), and [Lys0]gastrin-releasing peptide-27 (GRP) with cyanine 3.18 (cy3). Cy3-peptides purified by HPLC were fully active, determined by [Ca2+]i mobilization. Binding was specific because it was abolished by unlabeled peptides and receptor antagonists. Transfected cells yielded a log-fold greater cy3 intensity than control cells by FACS. Confocal microscopy of transfected cells and cultured enteric neurons showed that cy3-SP bound to surface receptors and was internalized. Internalization was observed in living cells by capture of sequential images. Recovery of surface binding sites was monitored by flow cytometry using cy3-SP. Thus, cy3 neuropeptides can be used to isolate and study receptor-bearing cells.
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PMID:Characterization of receptors using cyanine 3-labeled neuropeptides. 747 10

The distribution and concentration of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) immunoreactivities in the pancreas of cats with experimentally induced chronic pancreatitis and of age- and sex-matched controls were investigated. By narrowing the main pancreatic duct between the head and the body to approximately 25% of its normal diameter, we induced within 5 weeks chronic pancreatitis restricted to the body and tail. In control animals, peptide immunoreactive nerves were distributed to the islets, acini, and ducts; the latter were predominantly innervated by fibers immunoreactive for NPY, VIP, or CGRP. The vasculature received an abundant supply of NPY-, CGRP-, and, to a lesser extent, SP-containing axons. Within intrapancreatic ganglia, peptide immunoreactivities were identified in fibers and ganglion cells, with the exception of CGRP and SP immunostaining, which could be visualized only in fibers. In animals with chronic pancreatitis, the innervation pattern of each peptidergic system was comparable to that described in controls. However, there was a remarkable increase in the density and staining intensity of VIP and NPY immunoreactive fibers in the exocrine parenchyma and fibrous septa of the body and tail, where chronic pancreatitis developed. Fibers immunoreactive for CGRP and SP also were moderately denser than in controls, whereas those containing GRP immunoreactivity did not show any detectable changes. In addition, a marked increase of the immunostaining for VIP and, to a much lesser extent, for NPY and GRP, was observed in neurites supplying the head of the pancreas, which appeared devoid of histologically detectable pathological alterations. Radioimmunoassay analysis confirmed the immunohistochemical observations. The increased density of distinct peptidergic nerves in the pancreas with induced chronic pancreatitis might be the result of compensatory phenomena in response to the inflammatory process.
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PMID:Differential effects of experimentally induced chronic pancreatitis on neuropeptide immunoreactivities in the feline pancreas. 750 19

The gut is richly supplied with peptide-containing nervous elements. In the present immunocytochemical study the origin, occurrence and topographical distribution of nerves containing vasoactive intestinal polypeptide (VIP), enkephalin, substance P (SP), somatostatin, neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP) and galanin were investigated in the porcine small intestine. In order to study the origin (extrinsic or intrinsic) of the nerve fibers, specimens from autotransplanted and extrinsically denervated jejunum were examined. Furthermore, possible changes in the distribution of intrinsic neurons after extrinsic denervation were studied. In the control jejunum each nerve fiber population had its own characteristic topographic distribution. There was no overt difference in distribution pattern of peptide-containing nerve fibers and cell bodies between the transplanted and the control segment except that NPY-, SP- and CGRP-containing nerve fibers disappeared around blood vessels. Thus VIP-, somatostatin-, GRP-, enkephalin- and galanin-containing nerve fibers were visibly unchanged in the transplanted segment. The results support the view that the peptide-containing nerve fibers are mainly intrinsic in origin except the NPY-, SP- or CGRP-containing perivascular nerve fibers which are extrinsic to the gut wall. In addition, the results of the present study suggest that transplantation and extrinsic denervation have no major effect on the distribution pattern of the intrinsic neuronal systems.
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PMID:Peptide-containing neurons remain unaffected after intestinal autotransplantation: an experimental study in the piglet. 750 53

1. The pharmacological profile of GR71251, a new tachykinin receptor antagonist, and its effect on the responses evoked by stimulation of primary afferent fibres were studied in isolated spinal cord preparations of neonatal rats. Potential changes were recorded extracellularly from a lumbar ventral root (L3-L5). 2. Bath-application of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) at 0.01-3 microM to the spinal cord induced depolarization of the ventral root in normal artificial cerebrospinal fluid (CSF). The NK1 agonist, acetyl-Arg6-septide, and the NK3 agonist, senktide, at 0.01-3 microM, also had potent depolarizing actions whereas two NK2 agonists, beta-Ala8NKA4-10 and Nle10NKA4-10, showed little depolarizing effects at 1 microM. 3. GR71251 (0.3-3 microM) caused a rightward shift of the concentration-response curves for SP, acetyl-Arg6-septide and NKA with pA2 values of 6.14, 6.75 or 6.70, respectively. The effects of GR71251 were readily reversible within 15-30 min after its removal. By contrast, GR71251 (1-5 microM) had little effect on the depolarizing responses to NKB and senktide. 4. GR71251 (1-3 microM) did not depress the depolarizing responses to bombesin, neuromedin B and gastrin-releasing peptide in normal artificial CSF. 5. Application of capsaicin to the spinal cord induced a depolarizing response, which was partially depressed by GR71251 (3-10 microM). 6. In the isolated spinal cord preparation, intense electrical stimulation of a dorsal root evoked a slow depolarizing response of the contralateral ventral root of the same segment. A similar slow ventral root depolarization was evoked by electrical stimulation of the ipsilateral saphenous nerve in an isolated spinal cord-saphenous nerve preparation. GR71251 (0.3-10 microM) dose-dependently depressed these slow ventral root potentials.7. In the spinal cord-peripheral nerve preparation, conditioning stimulation of the saphenous nerve evoked an inhibition of the muscle nerve-evoked monosynaptic reflex lasting about 20 s. The late part of the inhibition was markedly depressed by GR71251 (1-3 microM).8. The present results indicate that GR71251 is a potent and specific antagonist for tachykinin receptors in the spinal cord. The present study further provides evidence for the involvement of SP and NKA in the slow ventral root depolarization and the prolonged inhibition of monosynaptic reflex that are evoked by primary afferent stimulation.
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PMID:Depression of primary afferent-evoked responses by GR71251 in the isolated spinal cord of the neonatal rat. 750 77

Receptors for regulatory peptides (hormones or neurotransmitters) play a pivotal role in the ability of cells to taste the rich neuroendocrine environment of the gut. Recognition of low concentration of peptides with a high specificity and translation of the peptide-receptor interaction into a biological response through different signalling pathways (adenylyl cyclase-cAMP or phospholipase C-phosphatidylinositol) are crucial properties of receptors. While many new receptors have been identified and thereafter characterized functionally during the 1980s, molecular biology now emerges as the privileged way for the structural characterization and discovery of receptors. Different strategies of receptor cloning have been developed which may or may not require prior receptor purification. Among cloning strategies that do not require receptor purification, homology screening of cDNA libraries, expression of receptor cDNA or mRNA in Xenopus laevis oocytes or in COS cells, and the polymerase chain reaction method achieved great success, e.g. cloning of receptors for cholecystokinin, gastrin, glucagon-like peptide 1, gastrin-releasing peptide/bombesin, neuromedin K, neuropeptide Y, neurotensin, opioids, secretin, somatostatin, substance K, substance P and vasoactive intestinal peptide. All these receptors belong to the superfamily of G-protein-coupled receptors which consist of a single polypeptide chain (350-450 amino acids) with seven transmembrane segments, an N-terminal extracellular domain and a C-terminal cytoplasmic domain. In this chapter, we have detailed the properties of three receptors which play an important role in digestive tract physiology and illustrate various signal transduction pathways: pancreatic beta-cell galanin receptors which mediate inhibition of insulin release and intestinal epithelial receptors for vasoactive intestinal peptide and peptide YY, which mediate the stimulation and inhibition of water and electrolyte secretion, respectively.
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PMID:Receptors for gut regulatory peptides. 751 Sep 49

The expression of three enteric neuropeptides was examined in freshly dispersed ganglia and in ganglia cultured for up to 28 days. During culture, glial cells grew into a flat sheet surrounding a cluster of neurons identified with neuron-specific enolase (13 +/- 2/ganglion), which remained constant throughout the period of culture. The neurons underwent a distinctive temporal change, resulting in overexpression of substance P (SP), normal expression of somatostatin, and virtual suppression of vasoactive intestinal peptide (VIP). Three weeks after the start of culture, the ganglia contained and released (in response to 55 nM KCl, 0.1 mM 1,1-dimethyl-4-phenylpiperazinium, or 1 microM gastrin-releasing peptide) twice as much SP as freshly dispersed ganglia, corresponding to a sevenfold increase per cultured neuron; content and release of somatostatin did not change. SP content and release declined to 1.5% of those found in control cultures when nonneuronal cells were suppressed with cytosine arabinoside but were partially restored (13-17% of control) by nerve growth factor. In marked contrast, VIP was minimally (< 1%) present in and released from ganglia after the third day in culture. Suppression of VIP could reflect a selective loss of VIP neurons and/or VIP expression.
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PMID:Differential expression of substance P, somatostatin, and VIP in neurons from cultured myenteric ganglia. 752 Nov 37


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