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 ability to assess the importance of secretin in various physiological processes is limited by the lack of specific potent antagonists. Recently, reduced peptide bond (psi) analogues of bombesin or substance P in which the -CONH- bond is replaced by -CH2NH- are reported to be receptor antagonists. To attempt to develop a new class of secretin receptor antagonists, we have adopted a similar strategy with secretin and sequentially altered the eight NH2-terminal peptide bonds, the biological active portion of secretin. In guinea pig pancreatic acini, secretin caused a 75-fold increase in cyclic AMP (cAMP). Secretin inhibited 125I-secretin binding with a half-maximal effect at 7 nM. Each of the psi analogues inhibited 125I-secretin binding. [psi 4,5]Secretin was the most potent, causing the half-maximal inhibition at 4 microM, and was 2-fold more potent than the [psi 1,2]secretin; 7-fold more than [psi 3,4]secretin, [psi 5,6]secretin, and [psi 8,9]secretin; 9-fold more than [psi 7,8]secretin; 13-fold more potent [psi 6,7]secretin, and 17-fold more than [psi 2,3]secretin. Secretin caused a half-maximal increase in cAMP at 1 nM. At concentrations up to 10 microM, [psi 2,3]secretin, [psi 4,5]secretin, and [psi 8,9]secretin did not alter cAMP whereas [psi 1,2]secretin and [psi 6,7]secretin caused a detectable increase in cAMP at 10 nM, [psi 7,8]secretin at 300 nM, [psi 5,6]secretin at 1 microM, and [psi 3,4]secretin at 10 microM. The [psi 4,5], [psi 2,3], and [psi 8,9] analogues of secretin each inhibited 1 nM secretin-stimulated cAMP as well as [psi 3,4]secretin, which functioned as a partial agonist. [psi 4,5]Secretin was the most potent, causing half-maximal inhibition at 3 microM whereas [psi 8,9]secretin was 6-fold less potent, and [psi 2,3]secretin and [psi 3,4]secretin were 17-fold less potent. [psi 4,5]Secretin inhibited secretin-stimulated cAMP and binding of 125I-secretin in a competitive manner. [psi 4,5]Secretin did not interact with cholecystokinin, bombesin, calcitonin gene-related peptide, or cholinergic receptors but did interact with receptors for vasoactive intestinal peptide, causing half-maximal inhibition at 72 microM and thus had a 18-fold higher affinity for secretin than vasoactive intestinal peptide receptors. These results indicate that reduced peptide bond analogues of the NH2 terminus of secretin represent a new class of secretin receptor antagonists. It is likely that in the future even more potent members of this class can be developed which may be useful to investigate the role of secretin in various physiological processes.
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PMID:Reduced peptide bond pseudopeptide analogues of secretin. A new class of secretin receptor antagonists. 170 23

Neuropeptide Y (NPY), neurotensin (NT), substance P (SP) and vasoactive intestinal peptide (VIP) are four structurally unrelated neuroendocrine peptides which affect anterior pituitary function. All four peptides appear to be locally synthesized in the anterior pituitary gland and have been shown to be regulated by thyroid and/or sex hormone status. We show here that NT, SP and VIP but not NPY are influenced by adrenal hormone status in the male rat pituitary gland. Adrenalectomy increased the content of VIP (35.4 +/- 4.0 (S.E.M.) vs control 11.9 +/- 1.1 pmol/g wet weight) but decreased that of SP (18.8 +/- 2.3 vs control 36.7 +/- 3.5 pmol/g wet weight). Adrenalectomy combined with castration decreased the content of SP (14.6 +/- 3.5 vs control 36.7 +/- 3.9 pmol/g wet weight) but had no effect on VIP content. Treatment with dexamethasone produced significant decreases in NT, SP and VIP contents (17.8 +/- 2.3 vs control 32.6 +/- 3.4 pmol/g wet weight, 5.5 +/- 0.9 vs control 36.7 +/- 3.9 pmol/g wet weight and 4.2 +/- 0.6 vs control 11.9 +/- 1.1 pmol/g wet weight respectively). The changes in pituitary peptide contents occurred in parallel with changes in mRNA levels, suggesting that alterations in glucocorticoid hormone status can alter the synthesis of these peptides. These results, together with the known effects of these neuroendocrine peptides suggest possible functions for locally produced SP and VIP in regulating the secretion of adrenocorticotrophin and/or other pro-opiomelanocortin-derived peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of adrenal hormone status on neuroendocrine peptides in the rat anterior pituitary gland. 170 43

The arrangement of the enteric nerve plexuses in the colon of the guinea-pig and the distributions and projections of chemically specified neurons in this organ have been studied. Immunoreactivity for neuron specific enolase was used to examine the total population of neurons and individual subpopulations were studied using antibodies raised against calbindin, calcitonin gene-related peptide (CGRP), leu-enkephalin, gastrin releasing peptide (GRP), galanin, gamma aminobutyric acid, neurokinin A, neuropeptide Y (NPY), somatostatin, substance P, tyrosine hydroxylase and vasoactive intestinal peptide (VIP). Neuronal pathways within the colon were lesioned using myotomy and myectomy operations and extrinsic pathways running between the inferior mesenteric ganglia and the colon were also severed. Each of the antibodies revealed nerve cells and nerve fibres or only nerve fibres within the wall of the colon. VIP, galanin and GRP were in anally projecting pathways in the myenteric plexus, as they are in other species. In contrast, there are differences in the projection directions of enkephalin, substance P, NPY and somatostatin nerve fibres between regions and species. Surprisingly, somatostatin and NPY fibres have opposite projections in the small intestine and colon of the guinea-pig. The majority of nerve fibres that innervate the circular muscle, including fibres with immunoreactivity for VIP, enkephalin, substance P, NPY, galanin and GRP come from the myenteric ganglia. The mucosa is innervated by fibres from both the myenteric and submucous ganglia. The present results suggest that the guinea-pig distal colon is a suitable place in which to determine relations between structure, neurochemistry and functions of enteric neural circuits.
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PMID:Projections of chemically-specified neurons in the guinea-pig colon. 170 5

It is presumed today that spinal cord stimulation induces local delivery of vasoactive substances, such as prostacyclins, histamine, substance P, and vasoactive neuropeptides, in the perivascular environment and the vascular wall to mediate the segmental vasodilator response. To investigate this mechanism, 9 dogs were subjected to low thoracic spinal cord stimulation. Venous and arterial blood samples from the paraesthesic area in the lower limbs were obtained before and 120 min after stimulation to measure changes in the plasma concentration of vasoactive intestinal peptide, substance P, and histamine. The results were compared with those obtained from vessels of the upper limbs. Blood flow changes following stimulation were recorded by electromagnetic flowmeters. Local arterial vasoactive intestinal peptide showed a mean increase of 33% after 60 min of stimulation. Changes concerning substance P were inconclusive. Local arterial and venous histamine concentrations increased 26 and 29%, respectively, after 60 min of stimulation.
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PMID:Role of vasoactive substances in the segmentary vasomotor response following spinal cord stimulation. An experimental study. 170 85

1. The long-term influence of substance P (SP) and vasoactive intestinal peptide (VIP) on rat salivary gland weight was investigated after parasympathetic denervation or on feeding soft food. 2. The parotid gland lost about one-third of its weight within 4-5 days following parasympathetic post-ganglionic denervation or change in dietary regimen, from pellets to liquid diet, thought to reduce nerve reflex activity. 3. Daily i.v. infusions with SP or VIP diminished or largely prevented the fall in parotid gland weight, whereas infusions with pentagastrin, bethanechol and saline had no effect. The infusions were preceded by administration of alpha- and beta-adrenoceptor antagonists; these antagonists were also given to the control animals. 4. The effect of SP and VIP on the parotid gland weight appeared to be related to cell size rather than to cell number, as judged by measurements of RNA and DNA. 5. Observations on the two other major salivary glands underlined the fact that different gland types in the same animal behave differently. Parasympathetic preganglionic denervation (decentralization) lowered the weights of the sublingual and submandibular glands, whereas liquid diet only reduced the weight of the sublingual gland. SP and VIP did not affect the weights of the submandibular glands, but VIP prevented the slight fall in sublingual gland weight induced by liquid diet. 6. The present results suggest a trophic role in rats for SP and VIP on parotid glands and for VIP on sublingual glands. Such an influence may be exerted naturally as a result of their release from nerves containing these peptides around acini.
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PMID:Effects of repeated infusions of substance P and vasoactive intestinal peptide on the weights of salivary glands subjected to atrophying influences in rats. 170 5

This study examined the possibility that vasoactive intestinal peptide (VIP)- and substance P (SP)-containing nerve fibers in bronchial smooth muscle, glands, epithelium, and blood vessels originate from neurons of airway ganglia. Explants of airway walls were maintained in culture with the expectation that nerve fibers from neurons of airway ganglia would remain viable, whereas fibers originating from neurons not present in the airway walls would degenerate. Airways were dissected and placed into culture dishes containing CMRL 1066 medium for 3, 5, and 7 days. In controls (noncultured), VIP- and SP-like immunoreactivity was observed in nerve fibers associated with bronchial smooth muscle, glands, and blood vessel walls and in nerve cell bodies of airway ganglia. Nerve fibers containing SP were also observed within the bronchial epithelium. After 3, 5, and 7 days in culture, VIP- and SP-containing fibers were identified in all of the same locations except in the airway epithelium where SP-containing fibers could not be demonstrated. VIP and SP were frequently colocalized in the same nerve fibers of bronchial smooth muscle and glands in controls and cultured airways. There were no statistically significant differences in nerve fiber density for either VIP- or SP-containing fibers in bronchial smooth muscle between controlled and cultured airways. VIP concentrations in cultured airways were significantly less than in controls. The results suggest that a large proportion of VIP- and SP-containing nerve fibers supplying bronchial smooth muscle, glands, and blood vessels in the airways originate from neurons of airway ganglia.
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PMID:Distribution of vasoactive intestinal peptide- and substance P-containing nerves originating from neurons of airway ganglia in cat bronchi. 170

The ultimobranchial gland is an endocrine organ consisting of C cell groups. In chickens, the glands are richly supplied by nerve fibers immunoreactive for neurofilaments. It was found by immunocytochemical staining that C cells of chick ultimobranchial glands showed immunoreactivities for multiple kinds of neuropeptides and neuroendocrine proteins in addition to calcitonin, i.e., calcitonin gene-related peptide (CGRP), somatostatin, neurotensin, chromogranin A, and tyrosine hydroxylase. Furthermore, enkephalin-immunoreactive cells that showed long cytoplasmic processes and large cell bodies, being distinct from the C cell feature, were detected. The densities of these cells per unit area of ultimobranchial gland were assessed using computer-assisted image analysis system; calcitonin cells were 42.9 +/- 10.0%; CGRP cells 26.9 +/- 5.6%; neurotensin cells 8.6 +/- 6.9%; somatostatin cells 3.1 +/- 1.4%; chromogranin A cells 11.8 +/- 1.8%; tyrosine hydroxylase cells 10.0 +/- 5.2%; enkephalin cells 2.9 +/- 1.3%. Dense distributions of peptidergic nerve fibers were also detected in chick ultimobranchial glands. Numerous varicose fibers immunoreactive for substance P were distributed in the close vicinity to C cell clusters and blood vessels. Enkephalin-immunoreactive fibers were also prominent around C cell clusters. Galanin-, vasoactive intestinal peptide (VIP)-, and tyrosine hydroxylase-immunoreactive fibers were distributed around blood vessels only. Subsequently, the ontogeny of these neuropeptides, neuroendocrine proteins, and peptidergic innervations was examined in chickens at various developmental stages. In 10-day-old embryos, weak to moderately intense immunoreactivity for calcitonin was already present in almost all C cells. Immunoreactivities for somatostatin, CGRP, and tyrosine hydroxylase began to appear at this age. At 12 days of incubation, substance P-immunoreactive fibers were first detected in the parenchyma of ultimobranchial glands. Considerable numbers of enkephalin-immunoreactive fibers and cells were also observed. At 14 days of incubation, the largest populations of somatostatin- and enkephalin-immunoreactive cells were attained; the densities of somatostatin- and enkephalin-immunoreactive cells per unit area were 21.2 +/- 3.2% and 12.9 +/- 3.1%, respectively. Substance P-immunoreactive fibers became numerous throughout the gland at this age. Thereafter, calcitonin-, CGRP-, tyrosine hydroxylase-immunoreactive cells progressively increased in number with embryonic age, whereas somatostatin- and enkephalin-immunoreactive cells started to decrease. Chromogranin A- and neurotensin-immunoreactive cells began to appear at 16 days and 18 days of incubation, respectively. Galanin-, VIP-, and tyrosine hydroxylase-immunoreactive fibers were inconspicuous during embryonic life.
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PMID:Immunocytochemical localization and development of multiple kinds of neuropeptides and neuroendocrine proteins in the chick ultimobranchial gland. 170 88

Neuropeptides including SP and VIP modulate Ig secretion by in vitro stimulated lymphocyte cultures. It is not known whether these neuropeptides effect the B cell directly, or if they significantly alter humoral immune responses to pathogens. We have previously shown that granulomas derived from schistosome-infected mice contain immunoglobulin secreting B cells (ISC) as well as eosinophils that secrete substance P (SP) and vasoactive intestinal peptide (VIP). It therefore seemed plausible that B cells derived from infected animals might respond to these neuropeptides, and that such responses might effect immunoregulatory signals. In this study, we addressed these issues in the murine Schistosoma mansoni model, at the level of immunoglobulin secretion in single B cells. Spontaneous ISC were observed in both splenic and granuloma cell preparations. The addition of SP resulted in a dose-dependent reduction in the number and size of plaques (a 50% reduction was observed at 10(-9) M). This effect was blocked with SP antagonists. Similar results were observed in T cell-depleted cell cultures. VIP had no effect on ISC number or plaque size. We conclude that SP, but not VIP, decreases spontaneous ISC number and Ig secretion in short-term cultures of spleen and granuloma cells. SP appears to exert its effects at the level of single B cells through a receptor-mediated mechanism and may thus play an immunoregulatory role in schistosomiasis.
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PMID:Substance P but not vasoactive intestinal peptide modulates immunoglobulin secretion in murine schistosomiasis. 170 26

We have examined cells dispersed enzymatically from three different sites in the bovine lung (tracheal mucosa, bronchial mucosa and parenchyma) and the skin, in order to ascertain whether the bovine model could be used to study mast cell heterogeneity. Histochemically there were two sub-populations of mast cells present in both lung and skin (on the basis of toluidine blue staining and the sensitivity to formalin fixation), but their proportions were similar in all sites studied. Skin mast cells contained approximately twice the amount of histamine than their counterparts in the lung (P less than 0.05). Functional heterogeneity was examined by in vitro release of histamine following secretagogue challenge. Calcium ionophore induced a substantial release of histamine; skin mast cells releasing significantly more histamine than any of the lung mast cells (at 10 microM ionophore, 37.1% and 20.7% net histamine release, respectively, P less than 0.05), although the time-course of release from the two tissues was similar. The neuropeptides vasoactive intestinal peptide and somatostatin induced a modest but statistically significant release of histamine from both skin and lung mast cells, whilst substance P only induced histamine secretion from skin mast cells. A range of other potential immunological and non-immunological secretagogues was unsuccessful in eliciting histamine release from mast cells in any of the tissues. We conclude that there were no convincing histochemical differences between mast cells from the sites examined in the lung or skin. Additionally, there was no discernable functional heterogeneity between mast cells within the lung, but functional differences were evident between mast cells of the bovine lung and skin. However, in the absence of a suitable immunological stimulus the bovine model cannot be regarded as a good model of mast cell heterogeneity.
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PMID:Structural and secretory characteristics of bovine lung and skin mast cells: evidence for the existence of heterogeneity. 171 May 30

The distribution of chromogranin A (CgA), a soluble protein in dense-core synaptic vesicles expressed by a variety of neuronal cell types, was studied immunocytochemically in Alzheimer's disease and normal aging. In addition to its presence in neuronal perikarya and process, CgA-like immunoreactivity (CgA-li) was demonstrated in multiple dystrophic neurites forming the crown of senile plaques. Two different monoclonal antibodies, LK2H10 and PHE5, gave identical results. In the two regions of the brain studied--the calcarine cortex and the molecular layer of the dentate gyrus--the areal density of plaques associated with CgA-like immunoreactive neurites was greater than the density of Congo red-stainable amyloid cores, but smaller than the density of beta amyloid peptide deposits identified by the Campbell silver stain. By comparison, other synaptically released peptides--somatostatin 28, somatostatin 14, substance P, cholecystokinin, neurotensin, vasoactive intestinal peptide, and leu-enkephalin--were immunocytochemically detected in less than 30% of plaques. Thus CgA appears unique among known synaptically released substances in being present in dystrophic neurites in virtually all classic (i.e., Congo red stainable) plaques and additionally in a subpopulation of preamyloid plaques.
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PMID:Chromogranin A-like immunoreactive neurites are major constituents of senile plaques. 171 Jul 35


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