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)

In the search for novel antiproliferative agents for small cell lung cancer (SCLC), we found the neuropeptide antagonist [Arg6, D-Trp7,9,MePhe8]substance P(6-11) to be effective in vitro. In murine Swiss 3T3 cells [Arg6,D-Trp7,9,MePhe8]substance P(6-11) was identified as a potent inhibitor of vasopressin-stimulated DNA synthesis which also blocks [3H]vasopressin binding to specific cell-surface receptors. It was a less potent antagonist of gastrin-releasing peptide and bradykinin in these cells but did not block the effects of other mitogens. In SCLC cell lines, [Arg6,D-Trp7,9,MePhe8]substance P(6-11) inhibited colony-formation in soft agarose and growth in liquid culture in a dose-dependent manner. It also blocked receptor-mediated Ca2+ mobilization induced by vasopressin, bradykinin, cholecystokinin, galanin, gastrin-releasing peptide, and neurotensin. We suggest that broad-spectrum neuropeptide antagonists can block multiple autocrine and paracrine growth loops in SCLC and could be useful therapeutic agents.
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PMID:A neuropeptide antagonist that inhibits the growth of small cell lung cancer in vitro. 169 79

Two novel neuromedin C analogs [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C and [Leu9-psi-CH2NH-Leu10]neuromedin C, were synthesized by rapid solid phase methods and examined for their abilities to inhibit neuromedin C-stimulated amylase release by isolated rat pancreatic acini. Both analogs significantly inhibited maximally stimulated amylase release by neuromedin C in a dose-dependent manner with maximal inhibition seen at concentrations of 100 and 300 microM of [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C and [Leu9-psi-CH2NH-Leu10]neuromedin C, respectively. The IC50 (concentration required to half-maximally inhibit neuromedin C-stimulated amylase release) was 1.5 microM for [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C compared to a 13.4 microM IC50 for [Leu9-psi-CH2NH-Leu10]neuromedin C. The [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C analog produced a parallel rightward shift in the neuromedin C dose-response curve and Schild plots of the inhibition data gave a slope of 0.969 +/- 0.121 and a pA2 (apparent affinity for the acinar cell receptor in terms of neuromedin C receptor-stimulated amylase release) of 100 nM. While [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C significantly inhibited both neuromedin B- and gastrin releasing peptide-stimulated amylase release, the analog did not inhibit amylase release in response to either cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, carbamylcholine, the Ca2+ ionophore A23187, forskolin, or 8-bromo-cyclic AMP. The results demonstrate that [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C is a potent, specific, and competitive antagonist for neuromedin C and peptides of the gastrin releasing peptide family and may serve as a useful molecule for exploring the physiological role of these peptides.
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PMID:[D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C antagonizes neuromedin C-stimulated amylase release by acini isolated from the rat pancreas. 169 79

Biochemical mapping of five different peptide-like materials--calcitonin gene-related peptide (CGRP), substance P (SP), Met5-enkephalin (ME), cholecystokinin (CCK), and dynorphin A (1-8) (DYN)--was conducted in the dorsal and ventral zones of the spinal cord at the cervical, thoracic, and lumbar levels in 3-month-old rats 10 days after unilateral dorsal rhizotomy at the cervical level (C4-T2) or after neonatal administration of capsaicin (50 mg/kg s.c.). In control rats, all peptide-like materials were more abundant in the dorsal than in the ventral zone all along the spinal cord. However, in both zones, absolute concentrations of CGRP, SP, ME, and CCK were significantly higher at the lumbar than at the cervical level. Rhizotomy-induced CGRP depletion (-85%) within the ipsilateral dorsal zone of the cervical cord was more pronounced than that due to neonatal capsaicin (-60%), a finding suggesting that this peptide is contained in both capsaicin-sensitive (mostly unmyelinated) and -insensitive (myelinated) primary afferent fibers. In contrast, similar depletions of SP (-50%) were observed after dorsal rhizotomy and neonatal capsaicin treatment, as expected from the presence of SP only in the capsaicin-sensitive small-diameter primary afferent fibers. Although the other three peptides remained unaffected all along the cord by either intervention, evidence for the existence of capsaicin-insensitive CCKergic primary afferent fibers could be inferred from the increased accumulation of CCK (together with SP and CGRP) in dorsal root ganglia ipsilateral to dorsal root sections.
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PMID:Regional distribution of calcitonin gene-related peptide-, substance P-, cholecystokinin-, Met5-enkephalin-, and dynorphin A (1-8)-like materials in the spinal cord and dorsal root ganglia of adult rats: effects of dorsal rhizotomy and neonatal capsaicin. 169 86

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

Gastrin-releasing peptide (GRP) and bombesin can stimulate pepsinogen release by both gastrin-dependent and -independent mechanisms. Using isolated guinea pig gastric chief cells, we determined that GRP can act directly on the guinea pig chief cell to cause pepsinogen release. GRP and bombesin stimulated a 2.5- to 3-fold increase in pepsinogen release above basal release. Substance P also stimulated a small but significant increase in pepsinogen release. No gastrin immunoreactivity was detected in the supernatants of cells stimulated with up to 1 microM GRP or bombesin or 1 mM carbachol. GRP-stimulated pepsinogen release was completely inhibited by GRP/bombesin receptor agonists as well as substance P receptor antagonist but not by antagonists to receptors for gastrin, the octapeptide of cholecystokinin (CCK-8), secretin, vasoactive intestinal peptide (VIP), or muscarinic agents. Substance P-stimulated pepsinogen release was completely inhibited by substance P receptor antagonist but not by GRP/bombesin receptor antagonists. An additive effect on pepsinogen release was seen when GRP was combined with maximally effective concentrations of adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agents (VIP, secretin, 8-BrcAMP) but not with calcium-mediated agents (carbachol, CCK-8, gastrin). These results indicate that GRP can directly stimulate pepsinogen release from guinea pig chief cells by a specific GRP receptor that mobilizes intracellular calcium.
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PMID:Gastrin-releasing peptide directly releases pepsinogen from guinea pig chief cells. 170 Jun 25

The immunoreactivity of anti-neuron-specific enolase (NSE) and anti-Leu-7 on formalin-fixed sections of human salivary gland neoplasms was determined by the avidin-biotin-peroxidase complex method. In addition, neuropeptides, such as vasoactive intestinal polypeptide, somatostatin, and substance P, in human salivary gland neoplasms were expressed, whereas other polypeptides, including glucagon, cholecystokinin, leu-enkephalin and calcitonin, were absent. When 182 paraffin-embedded examples of human salivary gland tumors, including 112 benign and 70 malignant neoplasms, were examined immunohistochemically, positive immunoreactivity was observed in: 51 cases with NSE (59%) and 46 cases with Leu-7 (54%) of 86 pleomorphic adenomas; 11 cases with Leu-7 (61%) of 18 Warthin's tumors; 7 cases with Leu-7 (58%) of 12 acinic cell carcinomas; 5 cases with NSE (31%) of 16 adenoid cystic carcinomas; 5 cases with NSE (42%) and 4 cases with Leu-7 (33%) of 12 adenocarcinomas; 4 cases with NSE (25%) and 6 cases with Leu-7 (38%) of 16 undifferentiated carcinomas. The other tumors, such as oxyphilic adenomas, basal cell adenomas, epidermoid carcinomas, and mucoepidermoid carcinomas, were nonreactive. Neuropeptides were observed in the neoplastic epithelial cells of certain tumors such as Warthin's tumors, acinic cell carcinomas, adenocarcinomas and undifferentiated carcinomas. These findings suggest the possibility that cells of neuroendocrine origin, present in certain neoplastic salivary gland epithelia may play a significant role in the histogenesis of human salivary gland neoplasms.
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PMID:Immunopathological study of neuropeptide expression in human salivary gland neoplasms. 170 3

Peptides have recently been found to function as neuromodulators or neuromediators within nociceptive pathways at central and peripheral sites. More complex and varied in their chemistry compared to "classical" low molecular weight monoamine neurotransmitters, peptides may nonetheless co-exist with these within a single neuron. The biological activity of a peptide results from an "address" segment that permits receptor binding and a "message" segment that initiates reactions within the cell. Opioid peptides (endorphins) are derived from three precursors and act by altering ionic fluxes of potassium or calcium across cell membranes. Nonopioid peptides active in nociception include calcitonin and its gene-related peptide C.G.R.P., bradykinin, substance P, somatostatin, cholecystokinin, and corticotropin-releasing hormone, among others. Ongoing investigations show significant responses of several peptide systems in experimental models relevant to vascular pain. Although the creation of novel peptide analogues has therapeutic promise, their present clinical use must be cautious in light of reports of neurotoxicity after intraspinal application of some of these compounds in animal models.
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PMID:Neuropeptides and pain. 170 17

The kinetics of the changes in the cytoplasmic Ca2+ concentration (Ca2+i) and amylase release were measured in fura-2-loaded pancreatic acinar cells and perifused pancreatic acini, respectively. Cholecystokinin octapeptide (CCK-8) and its amphibian analogue caerulein induced similar dose-related increases of Ca2+i and amylase secretion with threshold concentrations of 2-6 x 10(-12) M, and maximal effects at 2 x 10(-10) M. The action of CCK/caerulein on Ca2+i was complex and similar to that of carbachol and bombesin with a prompt several-fold increase within seconds followed by a gradual decline over more than 5 min to a new sustained suprabasal level. The kinetics of amylase release in response to CCK and carbachol correlated with the changes in Ca2+i. Additions of the antagonists N2,O2-dibutyrylguanosine 3':5'-cyclic monophosphate and atropine after 30 min of CCK-8 and carbachol stimulation, respectively, were associated with prompt lowerings of Ca2+i and inhibitions of amylase secretion. The patterns observed with substance P (SP) and eledoisin were different with high concentrations (10(-8)-10(-7) M) giving monophasic increases of Ca2+i and amylase release. An initial stimulation of cells with a high dose of CCK eliminated the Ca2+i response to further stimulation with CCK, carbachol, bombesin and SP, whereas cells subjected to initial stimulation with SP responded to subsequent exposure to CCK with prolonged elevation of Ca2+i. The data indicate that stimulation with CCK, carbachol and bombesin may be associated with intracellular mobilization of calcium from more than one pool, and that an increase of Ca2+i is involved even in threshold stimulation of amylase release.
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PMID:Stimulation of pancreatic amylase release is associated with a parallel sustained increase of cytoplasmic calcium. 170 10

The effects of calcitonin gene-related peptide (CGRP) on acetylcholine (ACh) release from myenteric plexus neurons in primary culture were investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase in [3H]ACh release. The ACh release caused by CGRP was significantly inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was increased more than threefold by preincubation with theophylline. Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced [3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium or substance P but not by cholecystokinin octapeptide or forskolin. The results demonstrate that CGRP cause release of ACh from guinea pig myenteric plexus neurons and suggest that the peptide acts through an adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves neuronal calcium channels.
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PMID:Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide. 170 74

Using sequence-specific radioimmunoassays the occurrence of 4 neuropeptides (cholecystokinin (CCK), gastrin, somatostatin, substance P and some of their precursors) was examined in 19 human acoustic nerve tumors and corresponding normal tissue. The normal acoustic nerve tissue obtained by autopsy contained traces of CCK, somatostatin, and substance P (less than or equal to 0.5 pmol/g), but neither proCCK, gastrin nor progastrin. In contrast 8 tumors expressed proCCK (range 0.2-4.5 pmol/g), 3 tumors gastrin (0.1-7.3 pmol/g) and 14 tumors progastrin (0.6-2.2 pmol/g). Traces of somatostatin were present in two and substance P in one tumor. The results show that acoustic neuromas often express the homologous CCK and gastrin genes, but process their propeptides poorly to transmitter-active peptides. The tumor synthesis of gastrin/progastrin contrasts to the rare, sporadic expression of the gastrin gene in normal nerve tissue.
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PMID:Gastrin, cholecystokinin and their precursors in acoustic neuromas. 170 42


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