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)

Several peptides of the tachykinin family are reviewed. Special attention is spared to mammalian tachykinins as peptide neurotransmitters. Conformational possibilities of the tachykinins are considered in connection with their ability to interact with specific receptors. The results of theoretical and experimental studies suggest a significant identity of spatial structures of the tachykinins and explain the absence of the strict specificity in tachykinin-receptor interactions.
Mol Biol (Mosk)
PMID:[Tachykinins and conformational aspects of their interactions with receptors]. 132 1

1. The effects of retinoic acid, gamma-interferon, cytosine arabinoside, nerve growth factor, tumor necrosis factor, and 12-O-tetradecanoylphorbol 13-acetate on the human neuroblastoma cell line, LAN-5, were studied. Intracellular levels of acetylcholinesterase, neuron-specific enolase, catecholamines and related neurotransmitters, vasointestinal peptide, and substance P were evaluated after induction. 2. Cell morphology was strongly affected by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. The main effects of retinoic acid and gamma-interferon were the loosening of cell clusters and the extension of long neurites; cytosine arabinoside induced cell body swelling and marked neuritogenesis. Following 12-O-tetradecanoylphorbol 13-acetate treatment, the cells became small, round, and neuritic. Conversely, modifications induced by nerve growth factor and tumor necrosis factor were mild. Cell proliferation rate was reduced by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate, while nerve growth factor and tumor necrosis factor were devoid of effects. 3. Acetylcholinesterase activity was significantly stimulated by retinoic acid and by gamma-interferon. Neuron-specific enolase activity was unaffected by all treatments except 12-O-tetradecanoylphorbol 13-acetate, which enhanced it by 1.6-fold. 4. The cellular catecholamine and related metabolite content was lowered by retinoic acid and gamma-interferon, while cytosine arabinoside and, even more, 12-O-tetradecanoylphorbol 13-acetate showed a stimulatory activity on their intracellular accumulation. 5. Finally, the cell-associated vasointestinal peptide level was strikingly increased by gamma-interferon and, to a lesser extent, by retinoic acid, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. 6. It is concluded that the most relevant biochemical changes associated with LAN-5 cells differentiation involve the repertoire of neurotransmitters and neuropeptides. These events vary in quality and in quantity, likely due to the pattern complexity of gene expression triggered by each inducer in determining the diversity of neuronal phenotypes.
Cell Mol Neurobiol 1992 Jun
PMID:A combined evaluation of biochemical and morphological changes during human neuroblastoma cell differentiation. 135 48

1. Using an immunocytochemical procedure a wide range of immunoreactive vertebrate bioactive peptides (BAPs) has been found in hemocytes of Viviparus ater: bombesin, calcitonin, CCK-8, CCK-39, GH, glucagon, insulin, oxytocin, neurotensin, secretin, serotonin, somatostatin, substance P, vasopressin, and VIP. 2. No immunostaining was observed for antigastrin and antithyroglobulin antibodies. 3. The presence of BAP-like molecules in hemocytes suggests a correlation between hemocyte and APUD cells and is evidence of a relationship between the neuroendocrine and the immune systems.
Cell Mol Neurobiol 1992 Oct
PMID:The presence of immunoreactive vertebrate bioactive peptide substances in hemocytes of the freshwater snail Viviparus ater (Gastropoda, Prosobranchia). 136 24

In homogenates of guinea pig lung, binding of 125I-Bolton-Hunter-labeled substance P (BHSP), Bolton-Hunter-labeled eledoisin (BHELE), and [125I]iodohistidyl neurokinin A (INKA) was investigated. Equilibrium dissociation constants (derived from "cold" saturation experiments) for BHSP, INKA, and BHELE were 0.96 +/- 0.15, 1.61 +/- 0.26, and 1.98 +/- 0.12 nM, respectively. Specific binding of all three radioligands was increased 2-3-fold by 10 microM phosphoramidon. The rank order of potency of unlabeled tachykinins in competing against BHSP was substance P (SP) greater than [Sar9,Met(O2)11]-SP greater than SP methyl ester greater than neuropeptide gamma greater than neurokinin A greater than or equal to neurokinin B = kassinin greater than or equal to eledoisin greater than or equal to scyliorhinin II much greater than neuropeptide K, indicating binding to sites with the general characteristics of NK1 receptors. Similar rank potency orders were observed for INKA and BHELE, showing binding to NK1 sites, rather than to NK2 or NK3 sites, which are labeled with high affinity by these radioligands in other tissues. For all radioligands, competition curves for SP and the NK1-selective agonist [Sar9,Met(O2)11]-SP could be resolved into two components, representing high and low affinity binding sites. These were present in the approximate ratios 2:3 (for BHSP), 1:1 (for INKA), and 8:1 (for BHELE). Other agonist competition curves also yielded high and low affinity components. The data suggest that BHSP and INKA bind partly and BHELE predominantly to high affinity NK1 receptors. The nature of the low affinity site(s) could be another tachykinin receptor or a low affinity state of the NK1 receptor. Binding to a "classical" NK2 receptor is unlikely, because selective NK2 receptor antagonists and analogs were very weak competitors. Our data suggest that, in addition to the NK1 receptor, another type of tachykinin receptor may exist in this tissue. The inability to detect NK2 binding sites is strikingly at variance with functional studies.
Mol Pharmacol 1992 Jan
PMID:Radioiodinated substance P, neurokinin A, and eledoisin bind predominantly in NK1 receptors in guinea pig lung. 137 Jul 5

The mechanism by which intracellularly applied guanosine-5'-O-(2-thiodiphosphate) alters responses to chicken II luteinizing hormone-releasing hormone, muscarine, and substance P in bullfrog sympathetic neurons was examined. Whole-cell recordings were made from enzymatically dissociated single neurons. Guanosine-5'-O-(2-thiodiphosphate) was applied intracellularly by adding it to the pipette solution with fixed amounts of GTP. Guanosine-5'-O-(2-thiodiphosphate) did not affect the proportion of cells that responded to any of the agonists. Guanosine-5'-O-(2-thiodiphosphate) decreased the amplitude of the responses to submaximal concentrations of agonist. At maximal concentrations of agonist, guanosine-5'-O-(2-thiodiphosphate) did not decrease the response to the first application of agonist; however, with guanosine-5'-O-(2-thiodiphosphate) intracellularly, successive responses to maximal concentrations of agonist were decreased in amplitude and increased in time course. Intracellular guanosine-5'-O-(2-thiodiphosphate) did not accelerate the rate or magnitude of desensitization to substance P. A kinetic model of receptor-guanine nucleotide-binding protein (G protein) coupling predicts that a decrease in the available G protein pool should decrease both the magnitude and the time course of the build-up of active G proteins. The results are consistent with the hypothesis that guanosine-5'-O-(2-thiodiphosphate) binds tightly to G proteins, thereby effectively decreasing the available G protein pool with repeated agonist applications.
Mol Pharmacol 1992 Mar
PMID:Intracellular guanosine-5'-O-(2-thiodiphosphate) alters the dynamics of receptor-mediated responses in bullfrog sympathetic neurons. 137 87

The neuropeptide galanin (GAL) has been detected in the peripheral and central nervous systems. However, little is known about its distribution and localization in heart, and the possible coexistence of GAL with other neuropeptides in the heart is not established. The present immunocytochemical study describes the distribution of GAL in nerves of the feline heart and its colocalization with vasoactive intestinal peptide (VIP), substance P (SP), and neuropeptide Y (NPY). GAL-like immunoreactivity was widely distributed in the atrial and ventricular myocardium and around coronary arteries. Colocalization of GAL with VIP, SP and NPY was observed in many nerve fibers. Further, GAL and NPY were colocalized in nerve cell bodies of intracardiac ganglia. Since these neuropeptides have been found to be associated with sensory and autonomic innervation in the heart, the present findings provide evidence that GAL is shared by functionally different neuronal populations in the heart and that GAL may participate in controlling cardiac function by combined action with other neuropeptides.
J Mol Cell Cardiol 1992 Jan
PMID:Distribution of the neuropeptide galanin in the cat heart and coexistence with vasoactive intestinal peptide, substance P and neuropeptide Y. 137 50

125I-Bolton-Hunter-substance P (125I-BH-SP) binding properties of three novel classes of neurokinin-1 (NK-1) receptor antagonists were investigated in tissues derived from humans, guinea pigs, and rats. 125I-BH-SP was shown to bind to a single class of binding sites, with similar dissociation constants, Kd, in human astrocytoma cells (U-373 MG), human urinary bladder, guinea pig forebrain, guinea pig ileum longitudinal smooth muscle, rat forebrain, and rat duodenum. In each tissue preparation, known peptide agonists and peptide antagonists yielded potencies typical for a NK-1 receptor profile, with little difference in binding properties between the various tissues. However, when the three classes of compounds, heterosteroids, cyanines, and modified peptides, were tested for their ability to displace 125I-BH-SP binding from the NK-1 receptor, very different binding profiles were observed. The heterosteroids were shown to be as much as 3 orders of magnitude more potent in tissues derived from rats than from humans or guinea pigs. A distinct species-dependent structure-activity relationship (SAR) was also observed for this class of compounds. Like the heterosteroids, the cyanines displaced 125I-BH-SP with 10-30-fold higher affinity in rat tissues than in human and guinea pig tissues. However, the SAR generated by the cyanines was comparable in all tissues studied. The modified peptides, on the other hand, were up to 10-100-fold more potent in human and guinea pig than rat tissues, producing a SAR that differed between the various species. No differences in binding properties between central nervous system and peripheral tissues from the same species were seen with these compounds. These results provide evidence for species differences in NK-1 receptors in humans, guinea pigs, and rats. Because it is known that there exists great sequence identity between rat and human NK-1 receptors, it is hypothesized that key amino acid changes or different lipid environments within the transmembrane binding region of the receptor may account for the observed species difference. Furthermore, this study emphasizes that caution is necessary in the choice of species to be used in development programs targeted towards therapeutic entities in the NK-1 receptor antagonist area.
Mol Pharmacol 1992 Apr
PMID:Antagonists that demonstrate species differences in neurokinin-1 receptors. 137 2

The influence of cocaine self-administration on the expression of messenger RNAs for dynorphin, enkephalin and substance P was analyzed in the rat striatum with in situ hybridization histochemistry. Cocaine, an indirect dopamine agonist, was found to differentially affect the levels of mRNA encoding these neuropeptides in different subregions of the striatum. Following a 7 day period of variable free access to cocaine, dynorphin and substance P mRNA levels were elevated throughout the striatum, but the increases were substantially greater in the dorsal striatum than in the nucleus accumbens. Enkephalin mRNA was not significantly altered in the dorsal striatum but was slightly elevated in the nucleus accumbens. These results suggest that cocaine self-administration has differential effects on striatonigral and striatopallidal projection neurons, and that these effects vary in subregions of the striatum.
Brain Res Mol Brain Res 1992 Mar
PMID:Cocaine self-administration differentially alters mRNA expression of striatal peptides. 137 4

Indirect evidence links sensory nerves with mast cells (MC) in inflammatory reactions of airway, skin, and intestine. Isolated MC secrete histamine, serotonin, and other inflammatory mediators in response to neuropeptides such as substance P (SP) in vitro. To obtain direct evidence of nerve/MC interactions, we used a tissue culture model involving the co-culture of murine sympathetic neurons and rat basophilic leukemia (RBL) cells (homologous to mucosal MC). An electrophysiologic analysis of the consequences of neuron/RBL cell contacts showed that neurite contact with RBL cells reduced the control input resistance (Ro) of 61.8 +/- 3.2 (n = 110) M omega to 22.4 +/- 4.8 (n = 13) M omega (P less than 0.01) without change in the membrane potential. Time course studies showed that Ro of RBL cells with neurite contact was always lower by 30 to 54% than adjacent RBL cells lacking such contact. This effect was not seen in RBL cells cultured on rat fibroblasts. Direct application of SP, bradykinin, and somatostatin, but not acetylcholine, noradrenaline, or the putative neurotransmitter ATP, could partly mimic the effect of neurite contact. Therefore, neurotransmitter release from sympathetic neurons in contact with RBL cells may decrease RBL cell membrane resistance, possibly leading to activation.
Am J Respir Cell Mol Biol 1992 May
PMID:Sympathetic nerve contact alters membrane resistance of cells of the RBL-2H3 mucosal mast cell line. 137 18

We have measured the affinity of various analogs and fragments of the tachykinin substance P for the cloned rat NK1, NK2, and NK3 receptors heterologously expressed in Chinese hamster ovary cells. The hydrophobic carboxyl-terminal pentapeptide sequence substance P-(7-11) binds with similar affinity (2-20 microM) to all three receptors. Our data suggest that addition of one to three amino-terminal residues to this sequence results in the optimization of its interaction within the binding pocket of the NK1 receptor. The addition of Pro-Gln-Gln to the carboxyl-terminal pentapeptide sequence increases affinity for the NK1 receptor, either by providing additional binding interactions or by modifying the conformation of the carboxyl-terminal sequence. This latter hypothesis is supported by the observation that physalaemin and phyllomedusin, which also contain a proline residue in the position analogous to the proline residue 4 of substance P, are also selective for NK1 receptors. Tachykinins that lack this proline have no higher affinity for NK1 than [pGlu] substance P-(6-11). Conversely, addition of Pro-Gln-Gln to the carboxyl-terminal pentapeptide sequence is unfavorable for NK2 and NK3 receptor binding. Preliminary data suggest that tachykinins with high affinity (Kd less than 500 nM) for NK2 receptors contain an aspartate residue in the position analogous to residue 5 of substance P, suggesting that an ionic interaction with the receptor may contribute binding energy. Further experiments will be required to determine the structural determinants of the NK1, NK2, and NK3 receptors responsible for these binding properties.
Mol Pharmacol 1992 Jun
PMID:Determination of the amino acid residues in substance P conferring selectivity and specificity for the rat neurokinin receptors. 137 26


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