UNIPROT:P20366 - FACTA Search

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 comparative distribution of peptidergic neural systems in the brain of the euryhaline, viviparous teleost Poecilia latipinna (green molly) was examined by immunohistochemistry. Topographically distinct, but often overlapping, systems of neurons and fibres displaying immunoreactivity (ir) related to a range of neuropeptides were found in most brain areas. Neurosecretory and hypophysiotrophic hormones were localized to specific groups of neurons mostly within the preoptic and tuberal hypothalamus, giving fibre projections to the neurohypophysis, ventral telencephalon, thalamus, and brain stem. Separate vasotocin (AVT)-ir and isotocin (IST)-ir cells were located in the nucleus preopticus (nPO), but many AVT-ir nPO neurons also displayed growth hormone-releasing factor (GRF)-like-ir, and in some animals corticotrophin-releasing factor (CRF)-like-ir. The main group of CRF-ir neurons was located in the nucleus recessus anterioris, where coexistence with galanin (GAL) was observed in some cells. Enkephalin (ENK)-like-ir was occasionally present in a few IST-ir cells of the nPO and was also found in small neurons in the posterior tuberal hypothalamus and in a cluster of large cells in the dorsal midbrain tegmentum. Thyrotrophin-releasing hormone (TRH)-ir cells were found near the rostromedial tip of the nucleus recessus lateralis. Gonadotrophin-releasing hormone (GnRH)-ir cells were present in the nucleus olfactoretinalis, ventral telencephalon, preoptic area, and dorsal midbrain tegmentum. Molluscan cardioexcitatory peptide (FMRF-amide)-ir was colocalized with GnRH-ir in the ganglion cells and central projections of the nervus terminalis. Melanin-concentrating hormone (MCH)-ir neurons were restricted to the tuberal hypothalamus, mostly within the nucleus lateralis tuberis pars lateralis, and somatostatin (SRIF)-ir neurons were numerous throughout the periventricular areas of the diencephalon. A further group of SRIF-ir neurons extending from the ventral telencephalon into the dorsal telencephalon pars centralis also contained neuropeptide Y (NPY)-, peptide YY (PYY)-, and NPY flanking peptide (PSW)-like-ir. These immunoreactivities were, however, also observed in non-SRIF-ir cells and fibres, particularly in the mesencephalon. Calcitonin gene-related peptide (CGRP)-like-ir had a characteristic distribution in cells grouped in the isthmal region and fibre tracts running forward into the hypothalamus, most strikingly into the inferior lobes. Antisera to cholecystokinin (CCK) and neurokinin A (NK) or substance P (SP) stained very extensive, separate systems throughout the brain, with cells most consistently seen in the ventral telencephalon and periventricular hypothalamus. Broadly similar, but much more restricted, distributions of cells and fibres were seen with antisera to neurotensin (NT) and vasoactive intestinal peptide (VIP).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative distribution of neuropeptide-immunoreactive systems in the brain of the green molly, Poecilia latipinna. 208 20

The newly recognized class of 5-hydroxytryptamine receptors (5HT3) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT3 receptors are present on enteric neurons, and 5HT3 blockers may produce mild constipation; we thus hypothesized that 5HT3 receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT3 antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18-70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P less than 0.0005). Transit times through the left colon (P less than 0.0005) and rectosigmoid (P less than 0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P less than 0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. 213 32

The discovery of new peptides that may or may not be members of existing peptide families is stimulating research in the field of gastrointestinal motility. Before their function in control of human motility can be predicted, both anatomic and functional pathways must be determined in a number of animal models. In many instances this has just begun. In other instances old concepts must be revised. This review examines the recent findings that motor actions attributable to VIP and by extension to its colocalized family member PHI may occur by turning off a tonic release that has held the muscle in a relaxed state. For the opioid family, some of the very complex actions are probably attributable to its action to inhibit the tonic release of VIP. For the tachykinin/neurokinin family, the focus is on the potential role as a sensory transmitter released antidromically from afferent capsaicin-sensitive nerve endings. In summarizing the actions of galanin, the reader is cautioned against any extrapolation to other species, because the actions and structure of the peptides have been found to be different in each species examined. CGRP, again a sensory transmitter found colocalized with substance P, tends to exert an opposite action on the smooth muscle from substance P (that of relaxation), and the interactions between these peptides may well prove to be important in gastrointestinal reflexes. The PP, PYY, and NPY family require much more study in gastrointestinal motor systems but appear to act as presynaptic inhibitory transmitters in a variety of local motor reflexes. One caveat from one who studies these systems is never to predict the action of a new or old peptide in your system of study, because the complexity of the system appears to determine the action expressed.
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PMID:Control of gastrointestinal motility by peptides: old peptides, new tricks--new peptides, old tricks. 247 97

Nervous and endocrine peptidergic structures in human Brunner's glands were studied by immunofluorescence. Endocrine cells storing immunoreactive components respectively similar to somatostatin 14, the amino-terminal portion (1-14) of somatostatin 28, gastrin-cholecystokinin, and peptide YY were distributed throughout the acini. Peptidergic nerve structures contained materials immunologically related to vasoactive intestinal peptide, peptide histidine methionine, substance P, neuropeptide Y, and gastrin-releasing peptide. The latter peptide was detected in discrete fibers running into the acini but within no cell body in the submucosa. All other neuropeptides were stored in fibers, isolated or grouped in bundles, and in perikarya of submucosal ganglia close to the acini. No immunoreactive structures were detected using antisera directed against pancreatic polypeptide, secretin, motilin, neurotensin, or calcitonin gene-related peptide. The results suggest that several regulatory peptides may be involved in the control of Brunner's glands in humans.
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PMID:Immunocytochemical study of peptidergic structures in Brunner's glands. 247 87

In this immunocytochemical study, we have analyzed the developmental profile and phenotypic expression of the endocrine cell antigens chromogranin, 5-hydroxytryptamine, gastrin/cholecystokinin, cholecystokinin (9-20), somatostatin, somatostatin 28 (1-14), somatostatin cryptic peptide, glucagon, glucagonlike peptides 1 and 2, glicentin, peptide YY, glucose-dependent insulinotropic peptide, secretin, neurotensin, and substance P in human fetal stomach and intestine. All currently identifiable endocrine cell types were detected by 10 wk of gestation. Immunostaining for the endocrine cell marker chromogranin revealed abundant endocrine cells in the earliest specimens (8 wk of gestation) with a relatively higher frequency in both proximal duodenum and distal colon/rectum compared with other areas. Quantification of endocrine cells showed an increase with age that was roughly parallel to the growth of the gut as a whole. These studies show that the diversity of the endocrine component of the gut appears to be established by 10 wk of gestation and that gut activity is preceded by the development of a fully differentiated endocrine component, which may subserve or even initiate the onset of functional maturity.
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PMID:Developmental profile of chromogranin, hormonal peptides, and 5-hydroxytryptamine in gastrointestinal endocrine cells. 272 79

Using 125I-labeled neuropeptide Y (NPY) and peptide YY (PYY), we demonstrated the existence of specific receptors for these peptides on rat dorsal root ganglion (DRG) cells grown in primary culture. Scatchard analysis of membrane homogenates indicated that the peptides bound to 2 populations of sites, with approximate affinities of 0.08 and 6.5 nM. Only low levels of binding were detected on sympathetic neurons cultured from the same animals or on a variety of neuronal clonal cell lines. The binding of 125I-NPY and 125I-PYY to DRG cell membranes was considerably reduced by the nonhydrolyzable analog of GTP, Gpp(NH)p. The major effect of Gpp(NH)p was to reduce the number of lower-affinity NPY binding sites without altering the number of high-affinity binding sites. NPY potently inhibited Ca2+ currents recorded under voltage clamp in rat DRG cells. Both the transient and sustained portions of the Ca2+ current were inhibited. The inhibitory effects of NPY were completely blocked following treatment of the cells with pertussis toxin. Depolarization elicited a large influx of Ca2+ into DRG neurons as assessed using fura-2-based microspectrofluorimetry. This influx of Ca2+ could be partially inhibited by NPY. Furthermore, NPY effectively inhibited the depolarization-induced release of substance P from DRG cells in vitro. Thus, NPY may be an important regulator of sensory neuron function in vivo.
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PMID:Neuropeptide Y modulates neurotransmitter release and Ca2+ currents in rat sensory neurons. 290 13

Functional and specific receptors for vasoactive intestinal peptide (VIP) (determined by their capacity to bind 125I-VIP and activate adenylate cyclase) and cyclic AMP-dependent phosphodiesterase activities were characterized in enterocytes of human fetal small intestine between 18 and 23 weeks of gestation. Half-maximal stimulation of the cyclase and inhibition of 125I-VIP binding in membrane preparations were respectively observed at 1.4 and 5 X 10(-10) M VIP. The peptides structurally related to VIP activated the cyclic AMP generating system at pharmacological doses (10(-7) M and above) in the following order of potency: VIP greater than PHI greater than GRF greater than secretin. Other peptides or test substances, including GIP, pancreatic glucagon, somatostatin-14, gastrin, CCK, neurotensin, pancreatic polypeptide, PYY, substance P, histamine and isoproterenol are inactive in this system, while the ubiquitous adenylate cyclase activators NaF, forskolin and prostaglandins were effective. These results, combined with the appearance of intestinal VIP in nerve fibers at 8 weeks and with the morphological and enzymatic maturation at 9-12 weeks of the intestinal mucosa, indicate that this neuropeptide may regulate either the differentiation or function of enterocytes during the early development of human intestinal mucosa.
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PMID:Vasoactive intestinal peptide receptor activity in human fetal enterocytes. 298 18

Electrical transmural stimulation evoked a transient contraction in the isolated mesenteric artery of the dog. This contraction was abolished by guanethidine or tetrodotoxin and was partially inhibited by prazosin. Noradrenaline was competitively antagonized by prazosin. Similarly, in the reserpine-treated artery, electrical transmural stimulation produced a transient contraction which was abolished by guanethidine or tetrodotoxin. However, prazosin failed to inhibit this contraction. The contraction to noradrenaline was not significantly different from the response it produced in control vessels. Tyramine (10(-5) M), which acts on sympathetic nerves to release noradrenaline, evoked a tonic contraction in the untreated artery. This contraction was abolished or markedly attenuated by prazosin or guanethidine. The response was not observed in the reserpine-treated artery, indicating that reserpine had depleted the nerves of noradrenaline. In the control vessel alpha,beta-methylene-ATP produced a transient contraction which was followed by a complete relaxation to the basal level. This contractile response was not significantly different in the presence of guanethidine or prazosin or in the reserpine-treated artery. After desensitization of the vessel to alpha,beta-methylene ATP (5 X 10(-6) M) the prazosin-resistant contractions induced by electrical transmural stimulation were abolished both in reserpine-treated and untreated arteries. Also the contractile responses to ATP and alpha-beta-methylene-ATP were abolished but the responses to tyramine (control vessels), noradrenaline and KCl were not affected. 8-Phenyltheophylline (10(-5) M) showed no inhibitory effect on the contractile responses to electrical transmural stimulation, tyramine, ATP or alpha,beta-methylene-ATP. 7. Neuropeptide Y, peptide YY, vasoactive intestinal polypeptide, bombesin and substance P (10-7 and 10-6 M for each peptide) caused no contractile response in the dog mesenteric artery. 8. These experiments provide further evidence that the sympathetic contraction of the isolated mesenteric artery of the dog induced by electrical transmural stimulation consists ofan adrenergic and a purinergic component and that the latter component is mediated through postsynaptic P2- purinoceptors.
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PMID:The effect of reserpine on sympathetic, purinergic neurotransmission in the isolated mesenteric artery of the dog: a pharmacological study. 303 38

In mammalian tissues the C-terminal amide structure has been found to occur only in neuroactive or hormonally-active peptides. About half known neuropeptide and peptide hormones have this unique chemical feature. Using a chemical detection method, a search for previously unknown peptides that possess the C-terminal amide structure in extracts of brain and intestine was carried out and a number of novel neuropeptides and hormonal peptides, designated neuropeptide Y, PHI, peptide YY, galanin and neuropeptide K were isolated. We recently performed a similar search in porcine pancreas and found a high concentration of a peptide having a glycine amide at its C-terminus. Here we report the isolation, primary structure and biological activity of this novel peptide. The 49-residue peptide strongly inhibits glucose-induced insulin release from the isolated perfused pancreas and was therefore named pancreastatin. It may be important in the regulation of insulin secretion and in the pathogenesis and treatment of diabetes mellitus.
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PMID:Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. 353 10

Carcinoid tumors of the middle ear are rare, with only three previously reported cases. The authors report the light and electron microscopic and immunohistochemical features of two carcinoid tumors that occurred in a 34-year-old female and a 21-year-old male. Both presented with unilateral hearing loss. By light microscopic examination, both were characterized by trabecula of tall columnar cells with basal nuclei and no mitotic activity. Electron microscopic examination demonstrated large numbers of pleomorphic neurosecretory granules, perinuclear aggregates of intermediate filaments, cell junctions, and surface microvillous processes. Some cells contained intermediate filaments forming tonofilaments and lacked secretory granules. These cells stained for cytokeratin by immunoperoxidase and separated the neuroendocrine cells from the underlying basal lamina. The cells in this tumor stained for the molluscan cardioexcitatory peptide. Cells in both tumors also stained for pancreatic polypeptide. Neither case stained for lysozyme, insulin, glucagon, somatastatin, gastrin, substance P, thyroid-stimulating hormone, adrenocorticotropic hormone, Met-enkephalin, Leu-enkephalin, neuropeptide Y, peptide YY, neurotensin, Bombesin, serotonin, neuron-specific enolose, glial and neural filaments, S-100 protein, cholecystokinin, beta-endorphin, beta-human chorionic gonadotropin, luteinizing hormone/follicle-stimulating hormone, vasoactive intestinal polypeptide, prolactin or calcitonin. Carcinoid tumor of the middle ear can be distinguished from paraganglioma and middle ear adenoma.
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PMID:Carcinoid tumors of the middle ear. 357 33

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