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)

Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals. Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor. In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified. [DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist. All of these antagonists had low affinity for the NMB receptor. Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists. D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists. No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist. These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs. These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different. These results indicate that the development of receptor subtype-specific peptide agonists or peptide antagonists for newly discovered receptor subtypes of gastrointestinal hormones/neurotransmitters may be difficult because the strategies developed for one well-studied subtype may not apply to the other even though it is structurally closely related.
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PMID:Peptide structural requirements for antagonism differ between the two mammalian bombesin receptor subtypes. 756 61

An intimate association of nerve fibers with the central lacteal endothelium was demonstrated in the duodenum and ileum of the monkey by immunohistochemistry and transmission electron microscopy. In the basal portion of the central lacteal, nerve fibers containing large cored vesicles and small clear vesicles were located closely beneath the lacteal endothelium. Identification of nerves was performed by immunohistochemistry using antisera against substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide, gastrin-releasing peptide and neuropeptide Y. These nerves contained immunoreactivities for SP and CGRP only. Some of the nerves, either singly or in a dense bundle, indented the endothelial cells to form a conspicuous cushion protruding into the lumen. The attenuated endothelium covering the cushion occasionally was failing, and the nerves were exposed to the lumen. Tight of occasionally subendothelial nerve terminals bundles formed a synapse-like association between themselves: a swollen axonal profile was invaginated by a finger-like projection of another axon, the latter being filled with synaptic vesicles. These results suggest that the central lacteal lymphatics might be afferently monitored, presumably with regard to the luminal pressure, and, at the same time, efferently modulated by these nerves.
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PMID:Nerve terminals associated with the central lacteal lymphatics in the duodenal and ileal villi of the monkey. 767 39

Bombesin and 10 bombesin-related peptides were administered intracerebroventricularly to conscious and freely moving rats. All peptides tested were found to elicit excessive grooming, especially scratching behavior. Bombesin itself had the most potent and long-lasting activity in eliciting scratching behavior. Naturally occurring peptides such as neuromedin B and gastrin-releasing peptide (GRP)-(18-27) were short-acting compared with exogenous peptides such as bombesin and synthesized analogs. Two phyllolitorins, a new bombesin subfamily, were also examined in this study. [Leu8]phyllolitorin induced more scratching than [Phe8]phyllolitorin and proved to be virtually equipotent to bombesin. Corticotropin-releasing factor (CRF) and substance P induced considerable excessive grooming, but both peptides were strikingly weak in inducing scratching behavior. It is suggested that (1) scratching represents a specific behavior commonly induced by bombesin-related peptides and (2) the relative potency to induce scratching behavior reflects the metabolic stability of the peptide, e.g. endogenous versus exogenous, shorter versus longer sequences, or chemical protection of N-terminus.
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PMID:Scratching behavior induced by bombesin-related peptides. Comparison of bombesin, gastrin-releasing peptide and phyllolitorins. 769 21

Pancreatic ganglia are formed by neural crest-derived precursors, are innervated by enteric neurons, and contain neuropeptides. In addition, the enzyme NADPH-diaphorase is located in a subset of enteric and pancreatic neurons. The expression of neural markers (GAP-43 and NC-1), neurotransmitter-related markers (including neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), galanin (GAL), dopamine beta hydroxylase (DBH), substance P (SP), calcitonin gene-related peptide (CGRP)), and NADPH-diaphorase was studied in the fetal and neonatal rat gut and pancreas (E12-P28) in situ and in vitro. NC-1, GAP-43 and DBH-immunoreactive cells were found in the primordial stomach on day E12, and in the pancreas on day E13, along with NPY in endocrine cells. Pancreatic NPY-immunoreactive neurons were detected by day E18. CGRP was seen in the foregut at day E12 but not in the pancreas until day E14. Other neuropeptides (SP, GAL, GRP and VIP) all appeared in the foregut earlier than in the pancreas. NADPH-diaphorase activity was first found in situ in foregut neurons on day E13, and in the pancreas on day E14, but seen in explants a day earlier. These observations show that development of neurons occurs earlier in the gut than in the pancreas, and that NADPH-diaphorase activity appears earlier than the immunoreactivities of the neuropeptides.
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PMID:Appearance of neuropeptides and NADPH-diaphorase during development of the enteropancreatic innervation. 772 Feb 14

Research work over the last ten years has identified a nonadrenergic, non cholinergic innervation in the upper and lower airways, in man and other animals. This innervation has two components: An excitatory bronchoconstrictor component, of which the neurotransmitters are peptides, substance P, neurokinin A, CGRP and gastrin-releasing peptide. A bronchodilating component known as inhibitor, of which the neurotransmitters are the vasoactive intestinal peptide and nitric oxide. Those neurotransmitters effect all the systems that are involved in allergic respiratory diseases, asthma and allergic rhinitis. They may therefore have a role to play in the physiopathology of these diseases.
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PMID:[Airway neuropeptides--what is their role in physiopathology?]. 774 59

The distribution of neuropeptide Y, substance P, vasoactive intestinal polypeptide, Leu5-enkephalin, bombesin/gastrin-releasing peptide, calcitonin gene-related peptide, somatostatin, cholecystokinin and catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase was studied immunohistochemically in nerve fibres supplying the bovine vagina and uterus. The nerves containing tyrosine hydroxylase or dopamine-beta-hydroxylase and neuropeptide Y-immunoreactivity were particularly numerous in both organs. Substance P, vasoactive intestinal polypeptide and Leu5-enkephalin-containing nerves were less numerous whereas somatostatin and calcitonin gene-related peptide-immunoreactive nerves occurred occasionally. Bombesin/gastrin-releasing peptide and cholecystokinin immunoreactivities were not present in nervous fibers of the bovine uterus and vagina. Generally, the immunoreactive nerve terminals, fibers, networks or nerve bundles were present below the serous membrane, between smooth muscle cells of muscular layers, around blood vessels, in the submucosal layer and below the luminal epithelium of the uterus and cervix.
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PMID:Peptidergic innervation of the bovine vagina and uterus. 777 Nov 84

To evaluate the utility of screening for multiple gastrointestinal peptides in the evaluation of patients with chronic diarrhea, we studied 193 patients referred for evaluation of chronic diarrhea and eight patients with known peptide-secreting tumors as a reference group. Fasting plasma samples were assayed for motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, vasoactive intestinal polypeptide, gastrin-releasing peptide, and calcitonin during a protocol evaluation for causes of chronic diarrhea. Although none of the referred patients were found to have tumors, abnormal levels of one or more peptides were found in 86 of 193 patients (45%). Abnormal plasma peptide levels were sometimes as high in these patients as in patients with known peptide-secreting tumors and would have led to mistaken diagnoses of tumors much more often than they would have led to correct diagnoses. The positive predictive value of elevation of any assayed peptide was < 2% at realistic prevalence rates for peptide-secreting tumors; the negative predictive value of a series of normal results was > 99%, but much of this was due to the rarity of these tumors. Patients with chronic diarrhea should not be screened routinely with a panel of plasma peptide assays in an effort to detect tumors; instead, peptide levels should be ordered selectively. Elevated fasting concentrations of the plasma peptides measured in this study are most likely epiphenomena due to diarrhea and should not be the sole basis for invasive diagnostic or surgical management of these patients.
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PMID:Diagnostic value of fasting plasma peptide concentrations in patients with chronic diarrhea. 792 45

The neurohormonal structures of two human intestines removed due to rejection 22 months and eight months after intestinal transplantation were studied by an indirect immunohistochemical method and compared with normal ileum. The distribution and density of neurons immunoreactive for tyrosine hydroxylase, substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal peptide, galanin, gastrin-releasing peptide, L-enkephalin, and somatostatin were examined. Mucosal endocrine cells immunoreactive for somatostatin, peptide YY, and glucagon were also examined. Extrinsic adrenergic fibers and perivascular fibers were absent in all intestinal layers of the failed grafts. The distribution of intrinsic neurons was unchanged; however, the density was decreased by one rank. Distribution of endocrine cells of the first graft was similar to the normal. Extrinsic fibers were not detected by immunohistochemistry in human small intestinal grafts following long-term survival and eventual rejection, while the immunohistochemical expression of intrinsic neural and endocrine transmitters were well preserved.
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PMID:Immunohistochemical study of enteric nervous system after small bowel transplantation in humans. 795 15

Hirschsprung's disease (HSCR) is characterized by a non-propulsive distal intestinal segment (usually colon) leading to a functional obstruction. An absence of ganglia in the affected segment explains the synonymous term "aganglionosis coli". The lack of peristalsis is partly due to a deficient intestinal smooth muscle relaxation based on an absence of non-adrenergic, non-cholinergic (NANC) inhibitory innervation. Morphological studies using conventional microscopy, immunohistochemistry and immunochemistry against general neuronal markers and neuropeptides have been used to characterize the disturbed NANC innervation in HSCR. An increased cholinergic and adrenergic innervation is registered in the aganglionic segment in spite of the lack of neuronal cell bodies: Neuropeptides like vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), gastrin-releasing peptide (GRP), calcitonin gene-related peptide (CGRP), substance P (SP), enkephalins and galanin immunoreactive nerve fibres are all reduced in number in the aganglionic segment. In contrast, neuropeptide Y (NPY)-containing nerve fibres are increased in number in the diseased segment, probably reflecting the adrenergic hyperinnervation. General neuronal markers including chromogranins have been used to map the neuronal network in the HSCR intestine and also to investigate the endocrine cell system in the intestinal mucosa. Nitric oxide is a potent component of the NANC inhibitory innervation and its synthesizing enzyme, nitric oxide synthase (NOS), is shown to be almost absent in the neuronal system in aganglionic intestine.
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PMID:Hirschsprung's disease--immunohistochemical findings. 798 7

Medullary thyroid carcinoma (MTC) can be important for gastroenterologists because 20-30% of patients with MTC suffer from chronic diarrhea and the tumor is capable of producing--besides other bioactive substances--a multitude of gastroenteropancreatic hormones. Gastrointestinal hormone profiles of 5 patients with MTC were determined both basally and after intravenous stimulation with secretin and calcium respectively. Diagnosis of MTC was confirmed histologically or cytologically and by demonstration of elevated serum concentration of calcitonin both basally and after calcium stimulation. 4/5 patients had chronic diarrhea. Normal values or only borderline increases were found for the following hormones: vasoactive intestinal polypeptide (VIP), neurotensin, substance P, growth hormone releasing hormone (GRH), glucagon, neurokinin A, peptide YY, and pancreatic polypeptide. Somatostatin was elevated after calcium stimulation in 1/5 patients only. The main findings were increased basal concentrations for GAWK in 5/5 patients and elevated concentrations for gastrin-releasing peptide (GRP, human bombesin) after calcium stimulation in 4/5. Probably as a consequence of the GRP increase, an increase in gastrin occurred in parallel, indicating bioactivity of the GRP released from the tumor. Besides calcitonin as the main tumor marker for MTC, determination of GAWK and GRP seems to provide helpful additional markers in laboratory diagnosis of MTC. GRP determination after i.v. calcium infusion allowed identification of patients with normal basal plasma GRP concentration.
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PMID:[Gastrointestinal hormone profile in medullary thyroid carcinoma]. 801 6


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