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)

We have used the method of subtractive hybridization to isolate cDNA clones of mRNAs expressed in abundance in the visual cortex of 30-day-old kittens but absent or in lower abundance in the adult cat visual cortex. Of 12,000 colonies screened, 200 clones which hybridized to the subtracted probe were isolated and characterized. Northern blots confirmed the specificity of the vast majority of the isolated clones. 120 of the 200 clones were sequenced and the EMBL and GenBank (release 76) database were searched for known identities using FASTA and BLAST programs. Twenty-seven of these sequenced clones were identifiable. The identities showed that these sequences code for proteins involved in a variety of cellular processes. These include cell-cell interaction (TAPA-1, contactin, tachykinin receptor, phospholipase A2), cellular remodeling (C1q beta isoform, heat shock protein), neurofilament assembly (alpha tubulin and alpha internexin), neurotransmitter release (VAMP-2, amphiphysin, carboxypeptidase E, scg 10 and proton channel), energy metabolism (mitochondrial hinge protein, ADP/ATP transporter, cytochrome oxidase subunits), RNA processing (helix destabilizing protein, ribonucleoprotein) and protein synthesis (eIF-4A initiation factor, ribosomal protein S27). The results show that gene expression in the kitten visual cortex differs rather little from that of the adult visual cortex since over 98% of the sequences appear common. The relatively rare kitten-specific sequences are likely to form the basis for the critical period plasticity in this system.
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PMID:Identification of cDNA clones expressed selectively during the critical period for visual cortex development by subtractive hybridization. 818 Aug 41

The (quinolizidin-1 alpha-yl)methanthiol (thiolupinine) was prepared and, utilizing the thiol group reactivity, several S-substituted derivatives were obtained among which was a group of 3-[(lupinylthio)methyl]indoles. Eight of the prepared compounds were subjected to a broad pharmacological screening that evidentiated for many of them good level of the following activities in vivo and in vitro: antiarrhythmic, local anesthetic, negative chronotropic on isolated atria, calcium antagonism on ileum and atria, inhibition of spontaneous contraction of isolated trachea, inhibition of guinea pig ileum contractions induced by angiotensin I and II, bradykinin and cholecystokinin, inhibition of platelet aggregation induced by PAF and ADP. Single compounds were remarkable for additional antagonistic activities: 4 against P1-purine receptor, 8 against substance P, 12 against methacholine and 13 strongly inhibited arachidonate induced platelet aggregation. Very peculiar was the ability of compound 6 to protect mice from PAF induced mortality.
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PMID:Thiolupinine and some derivatives of pharmacological interest. 821 67

Calcium signaling in fura-2 acetoxymethyl ester-loaded enteric glia was investigated in response to neuroligands; responses to ATP were studied in detail. Carbachol (1 mM), glutamate (100 microM), norepinephrine (10 microM), and substance P (1 microM) did not increase the intracellular calcium concentration ([Ca2+]i) in cultured enteric glia. An increasing percentage of glia responded to serotonin (4%; 100 microM), bradykinin (11%; 10 microM), and histamine (31%; 100 microM), whereas 100% of glia responded to ATP (100 microM). ATP-evoked calcium signaling was concentration dependent in terms of the percentage of glia responding and the peak [Ca2+]i achieved; responses were pertussis toxin insensitive. Based on responsiveness of enteric glia to purinergic agonists and peak [Ca2+]i evoked, ATP = UTP > ADP > beta, gamma-methyleneadenosine 5'-triphosphate >> 2-methylthioadenosine 5'-triphosphate = alpha,beta-methyleneadenosine 5'-triphosphate = AMP = adenosine, suggesting a glial P2U receptor. Depletion of D-myo-inositol 1,4,5-trisphosphate-sensitive calcium stores by thapsigargin (10 microM) abolished glial responses to ATP. Similarly, calcium responses were decreased 92% by U-73122 (10 microM), an inhibitor of phospholipase C, and 93% by the phorbol ester phorbol 12-myristate 13-acetate (100 nM), an activator of protein kinase C. Thus, cultured enteric glia can respond to neurotransmitters with increases in [Ca2+]i. Our data suggest that glial responses to ATP are mediated by a P2U receptor coupled to activation of phospholipase C and release of intracellular calcium stores.
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PMID:Enteric glia exhibit P2U receptors that increase cytosolic calcium by a phospholipase C-dependent mechanism. 859 30

The endothelium takes part in the regulation of vascular tone through the production of endothelium-derived relaxing and contracting factors. The L-arginine pathway within endothelial cells in the blood vessel wall is the source of production of the endogenous nitrovasodilator, nitric oxide (NO). The NO molecule has one unpaired electron and readily reacts with oxygen, superoxide radicals, or transition metals. Therefore the measurement of the concentration of NO in biological systems is a challenging analytical problem. NO is formed from L-arginine via constitutive NO synthase. It is released under basal conditions and in response to mechanical stimuli such as shear stress and in response to receptor-operated agonists such as bradykinin, serotonin, ADP/ATP, thrombin, histamine and substance P. NO is the mediator of endothelium-dependent relaxation in the circulation and exerts its effects by activating soluble guanylyl cyclase in vascular smooth muscle, which in turn leads to the formation of cyclic guanosine monophosphate (cyclic GMP) and to relaxation. In addition to its effect on vascular smooth muscle, NO is also released albuminally to interact with circulating platelets. Increases in cyclic GMP in platelets are associated with a decreased adhesion and aggregation. In endothelial cells, NO inhibits its own production as well as that of the vasoconstrictor peptide endothelin-1. Thus, endothelium-derived NO, through its vasodilator and anti-aggregatory properties, prevents vasospasm and thrombus formation in the circulation and thereby helps to maintain blood flow to vital organs such as the heart. Under certain conditions such as inflammation, NO may also be formed via inducible nitric oxide synthase by smooth muscle cells, endothelium and monocytes. Therapeutic nitrates also exert their effects by releasing NO from their molecules and activating soluble guanylyl cyclase. Their effects are particularly pronounced in arteries in which the release of NO is inhibited or impaired or in the absence of the endothelium. Thus, the endothelial L-arginine pathway plays an important protective role in the local regulation of blood flow and through its vasodilator and antiplatelet properties. Nitrates can at least in part substitute the endogenous nitrovasodilator in disease states with impaired formation of NO.
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PMID:[Nitric oxide: the endogenous nitrate in the cardiovascular system]. 876 25

A rapid and simple spin column assay has been used to study interactions of BiP with substance P (SP) and ATP. At 4 degrees C, the binding of SP to BiP requires ATP and a stable SP-BiP.ATP complex is formed. Nonhydrolyzable ATP analogues or ADP cannot replace ATP. Although ATP converts BiP dimers to monomers, the requirement for ATP for SP binding is not solely due to BiP dissociation, because purified BiP monomers also require ATP for peptide binding. At 37 degrees C, there is rapid binding of SP to BiP even in the absence of ATP and, in fact, ATP at concentrations above 5 microM causes release of SP from BiP. At this higher temperature, there is also rapid hydrolysis of ATP bound to BiP. These results extend our previous results (Brot et al., 1994) that indicated the formation, at low ATP concentrations, of a labile SP.BiP.ATP complex that, after ATP hydrolysis, resulted in a stable SP.BiP.ADP complex.
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PMID:Interaction of BiP with substance P and nucleotides. 886 87

This study monitored the extranuclear endogenous mono ADP-ribosylation of proteins. At least 10 proteins were ADP-ribosylated in a crude extract from control superior cervical ganglia, and 7 were labeled in control dorsal root ganglia; whereas in the diabetic rat the extent of labeling was reduced. These data suggest that proteins of peripheral ganglia are excessively ADP-ribosylated in vivo. Treatment of diabetic animals with silybin, a flavonoid with ADP-ribosyltransferase inhibitory activity, did not affect hyperglycemia, but prevented the alterations in the extent of mono-ADP-ribosylation of proteins. This effect was associated with the prevention of substance P-like immunoreactivity loss in the sciatic nerve. In the membrane fraction of sciatic nerve Schwann cells, at least 9 proteins were ADP-ribosylated, in diabetic rats the extent of labeling was increased. A comparable increase involving the same proteins was triggered by chronic nerve injury and by corticosteroid treatment. Silybin treatment of diabetic rats prevented such an increase. We propose that the inhibition of excessive protein mono-ADP-ribosylation by silybin prevented the onset of diabetic neuropathy, while the silybin effect on mono-ADP-ribosylation of Schwann cells is likely indirect and secondary to the improvement of diabetic axonopathy.
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PMID:Alterations of protein mono-ADP-ribosylation and diabetic neuropathy: a novel pharmacological approach. 888 32

Isolated myenteric ganglion networks were prepared from guinea pig ileum and were used in a perifusion protocol to examine the effects of interstitial adenosine on evoked release of substance P-like immunoreactivity (SPLI). The release of SPLI evoked by elevated extracellular K+ concentration was increased in the presence of tetrodotoxin (TTX), indicating tonic inhibition of SPLI release and revealing net inhibitory interganglionic transmission. Perifusion in the presence of the adenosine A1 receptor-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine enhanced evoked SPLI release, which was further enhanced in the additional presence of TTX, indicating that adenosine contributes some, but not all, of the overall inhibitory tone within the networks. In addition to neural release of adenosine per se, an additional source was investigated. Perifusion in the presence of alpha, beta-methylene-ADP plus guanosine 5'-monophosphate, which inhibits ecto-adenosinetriphosphatase (ATPase) activity, enhanced SPLI release, indicating that hydrolysis of released ATP contributes to the total interstitial nucleoside concentration and thereby to the overall inhibitory tone. It is concluded that endogenous adenosine, some of which arises from ATP metabolism, is an important contributor to the overall inhibitory tone present in myenteric ganglion networks.
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PMID:Endogenous adenosine inhibits evoked substance P release from perifused networks of myenteric ganglia. 903 74

The extranuclear endogenous mono-ADP-ribosylation of proteins was monitored in cellular preparations of retina, superior cervical ganglion, dorsal root ganglia and peripheral nerve. At least 6 protein fractions are ADP-ribosylated in the crude extract fraction from retina control preparations, while in diabetic rats the number of retina labeled proteins and the extent of labeling are highly reduced. In the superior cervical ganglion labeling was present in 10 proteins, in diabetics it was greatly decreased. Treatment of diabetic rats with silybin, a flavonoid mono-ADP-ribosyltransferase inhibitor, did not affect hyperglycemia, but prevented the alteration of extent of protein ADP-ribosylation. These data suggest that proteins of retina and peripheral ganglia are excessively ADP-ribosylated in vivo. The effects of silybin treatment on excessive mono-ADP-ribosylation of proteins was associated with the prevention of reduction of substance P-like immunoreactivity levels, that is typical of diabetic neuropathy. In the membrane fraction of sciatic nerve Schwann cells, at least 9 proteins were ADP-ribosylated, diabetes caused a marked increase of labeling. A comparable increase involving the same proteins is triggered by chronic nerve injury and by corticosteroid treatment. Silybin treatment of diabetic rats prevented such an increase. We propose that the inhibition of excessive protein mono-ADP-ribosylation by silybin prevented the onset of diabetic neuropathy. While the effects on Schwann cells is likely indirect and secondary to the improvement of diabetic axonopathy.
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PMID:Endogenous mono-ADP-ribosylation in retina and peripheral nervous system. Effects of diabetes. 919 68

Phoneutria nigriventer venom causes stimulation of capsaicin-sensitive primary afferent neurons in the rat dorsal skin, leading to neurogenic plasma protein extravasation due to the release of tachykinin NK(1) receptor agonist. In this study we further investigated the mechanisms involved in the venom-induced activation of capsaicin-sensitive primary afferent neurons. The plasma extravasation in response to venom intradermally injected was measured in Wistar rats as the local accumulation of i.v. injected 125I-labelled human serum albumin into skin sites. The tachykinin NK(1) receptor agonist, D-Ala-[L-Pro(9),Me-Leu(8)]substance P-(7-11) (GR73632; 10-100 pmol/site), induced a significant plasma leakage that was abolished by the selective tachykinin NK(1) receptor antagonist, (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2]octane chloride (SR140333; 1 nmol/site), whereas the leakage after venom (1-10 microgram/site) was significantly inhibited (but not abolished) by SR140333. The calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37), failed to further reduce the residual plasma extravasation induced by venom plus SR140333. The mu-opioid receptor agonist, [D-Ala(2), Me-Phe(4),Gly-ol(5)]enkephalin (DAMGO), and the local anaesthetic, lignocaine, had no effect on the venom-induced plasma extravasation. Similarly, the L-, N- and P/Q-type voltage-sensitive Ca(2+) channel blockers (verapamil, omega-conotoxin MVIIA and MVIIC, respectively) as well as the Na(+) channel blockers, tetrodotoxin and carbamazepine, had no effect on the venom-induced effect. Neither the systemic treatment nor the local injection of ruthenium red prevented the venom-induced plasma extravasation. However, the vanilloid receptor antagonist, N-[2-(4-chlorophenyl) ethyl]-1,3,4, 5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamide (capsazepine; 120 micromol/kg, i.v.), reduced by 48% (P<0.05) the venom (10 microgram/site)-induced plasma extravasation. A significant inhibitory effect was also observed with the P(2) purinoceptor agonists, adenosine 5'-triphosphate (ATP; 10 and 30 nmol/site) and adenosine 5'-diphosphate (ADP; 10 nmol/site). The involvement of histamine and/or 5-hydroxytryptamine (5-HT) in the venom-induced plasma extravasation was ruled out since neither histamine and 5-HT receptor antagonists nor depletion of mast cells by compound 48/80 affected the venom response. This was further supported by the failure of venom to degranulate in vitro peritoneal mast cells. In conclusion, only vanilloid receptors and P(2) prejunctional purinoceptors had an inhibitory effect on the neurogenic plasma extravasation evoked by P. nigriventer venom in rat dorsal skin.
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PMID:Involvement of vanilloid receptors and purinoceptors in the Phoneutria nigriventer spider venom-induced plasma extravasation in rat skin. 1072 73

Impairment in endothelial cell intracellular free calcium (Ca(i)) mobilization mechanisms may contribute to decreased nitric oxide (NO) biosynthesis and impaired vasorelaxation responses of endotoxemic guinea pigs to endothelium-dependent vasodilators. We tested this hypothesis using fura-2 microfluorometry to compare agonist-stimulated Ca(i) responses of aortic endothelial cells freshly dispersed from guinea pigs 16 h after intraperitoneal injection of Escherichia coli endotoxin (lipopolysaccharide, LPS; 4 mg/kg) or saline (CON). In the presence of normal extracellular Ca2+ (2 mmol/L), basal (non-stimulated) endothelial Ca(i) (340/380 nm fluorescence ratio, R) was not different between CON and LPS cells (1.1 +/- 0.03 and 1.1 +/- 0.03, respectively). However, exposure to ADP (10 micromol/L) produced a biphasic increase in Ca(i) that was markedly decreased in cells from LPS-treated animals (P < 0.0001). Peak ADP-stimulated Ca(i) responses averaged 2.2 +/- 0.21 in CON cells and 1.5 +/- 0.11 (P < 0.01) in cells dispersed from LPS-treated animals. Exposure to acetylcholine (ACh; 10 micromol/L) produced sustained increases in Ca(i) (R = 1.4 +/- 0.13) in CON cells; however, LPS abolished Ca(i) responses to ACh. Exposure of endothelial cells to substance P (100 nmol/L) produced a biphasic increase in Ca(i) that was not different between groups. In the absence of extracellular Ca2+ (plus 10 micromol/L EGTA), exposure to ADP (10 micromol/L) produced transient increases in Ca(i) (Ca2+ release) that were decreased in cells from LPS-treated versus CON animals. Exposure to ACh in zero Ca2+ (10 micromol/L) produced smaller increases in Ca(i) (peak R = 1.3 +/- 0.12) in CON cells (when compared to ADP); however, Ca(i) responses to ACh remained absent in cells from LPS-treated animals. Re-exposure to Ca2+ produced sustained ACh-induced Ca(i) responses (Ca2+ influx) in cells from CON, but not LPS-treated animals; LPS markedly impaired (P< 0.05) ADP-induced sustained Ca(i) responses. Our data demonstrate that in vivo LPS exposure elicits decreased agonist-stimulated endothelial Ca(i) responses primarily involving impaired Ca2+ influx mechanisms. Known dependence of endothelial agonist-stimulated NO synthesis on Ca(i) suggests that defects in cell Ca2+ mobilization may contribute to LPS-induced impaired NO biosynthesis and decreased endothelium-dependent relaxation.
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PMID:Endotoxin impairs agonist-stimulated intracellular free calcium (Ca(i)) responses in freshly dispersed aortic endothelial cells. 1133 99


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