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 light of current interest in substance P as a bronchoconstrictor, several pharmacologic antagonists of known mediators of anaphylaxis were tested for possible activity against this neuropeptide. Concentration-dependent contractions of the isolated guinea-pig tracheal strips to substance P (10(-8) to 10(-5) M) were elicited. These contractions were inhibited by substance P receptor antagonists, D-Arg1-D-Trp7,9-Leu11 and D-Pro2-D-Trp7,9-substance P (10(-6) to 10(-4) M). Substance P-induced contractions were not inhibited by histamine, alpha and beta adrenergic receptor antagonists or by cyclooxygenase inhibition. However, atropine enhanced contractions to substance P. Both vasoactive intestinal polypeptide (10(-7), 10(-6) and 10(-4) M) and isoproterenol (10(-7) M) were able to reverse an ongoing substance P (10(-5) M)-induced contraction. Also, at a concentration of 10(-5) M, substance P increased cyclic GMP accumulation, but had no effect on the concentration of cyclic AMP. A 15-min pretreatment with either verapamil or nifedipine (10(-8) M) had no effect on substance P-induced contractions, whereas the purported intracellular Ca++ antagonist, 8-[N,N-diethylamino]-octyl 3,4,5-trimethoxybenzoate hydrochloride (10(-4) M) produced a rightward shift of a substance P concentration-response curve. A selective calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (10(-4) M) failed to affect the contraction produced by 10(-5) M substance P. When guinea-pig tracheal strips were washed and allowed to re-equilibrate in 0 Ca++ buffer, the initial maximum contractions to substance P (10(-5) M) were equal for both regular (1.8 mM) Ca++ and 0 Ca++ buffer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of substance P-induced contractions of guinea-pig trachea. 242 83

Rat peritoneal mast cells were stained with quin 2, a fluorescent Ca2+ chelator. By means of a fluorescence microscope and real time image processer, it was revealed that the fluorescence derived from the Ca-quin 2 complex was weak in the area occupied by the nucleus and distributed unevenly in the cytoplasm of the resting cells so as to encompass the individual granules. When compound 48/80 or substance P was added in a Ca-free medium, the fluorescence intensity of quin 2 increased markedly all over the cell, suggesting that a large amount of Ca2+ was released from intracellular Ca stores. The increase in the fluorescence intensity produced by compound 48/80 or substance P in a Ca-free medium was inhibited by pretreatment with certain drugs eliciting an increase of c-AMP levels, such as dibutyryl c-AMP and theophylline, or by some anti-allergic drugs providing a membrane stabilizing action.
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PMID:Changes in intracellular Ca2+ distribution of rat peritoneal mast cells before and after histamine release. 242 94

Substance P (SP) receptors were described by the specific binding of [3H]SP to several neuronal and glial cell lines. The neuronal cell lines N18 and NG108-15 were found to contain few if any SP receptors (less than 5 fmol/mg of protein). The glial cell line LRM55 contained large numbers (Bmax = 707 fmol/mg of protein) of a single class of SP binding sites (Kd = 276 pM). [3H]SP binding could be inhibited by a number of c-terminal SP fragments and the tachykinins physalaemin, eledoisin and kassinin. The binding kinetics and pharmacology of these receptors are similar to those the authors have previously described in the brain. Activation of SP receptors was shown to inhibit cyclic AMP-dependent, beta adrenergic-stimulated taurine release from LRM55 glial cells. SP inhibition must occur by mechanisms affecting taurine release after adenylate cyclase activation, inasmuch as SP has no significant effect on beta adrenergic-stimulated increases or basal levels of intracellular cyclic AMP.
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PMID:Identification and characterization of substance P receptors on LRM55 glial cells. 242 40

We investigated the properties of the novel dorsal root ganglion (DRG) hybrid cell line F-11 to see how closely these cells resembled normal DRG cells. Under normal growth conditions, F-11 cells appeared to contain several short neurite-like processes. However, these cells could also be grown under conditions in which they showed a much more extensive neuronal morphology, exhibiting many long neurites. Several differentiated features of DRG cells were present on F-11 cells. These included the presence of delta-opioid receptors, receptors for prostaglandins and bradykinin, and dihydropyridine-sensitive calcium channels. F-11 cells also synthesized and released a substance P-like compound, as determined by immunoreactivity. Both the number of bradykinin receptors and the voltage-sensitive calcium influx increased on cell differentiation. Opioid agonists (delta-specificity) were found to decrease cyclic AMP levels in F-11 cells in a naloxone- and pertussis toxin-reversible fashion. Bradykinin stimulated the synthesis of inositol-1,4-bisphosphate and inositol-1,4,5-trisphosphate. Ca2+ channel agonists stimulated voltage-sensitive Ca2+ influx in a dose-dependent, stereospecific manner, whereas Ca2+ channel antagonists inhibited Ca2+ influx. F-11 cells should, therefore, prove useful as models for authentic DRG neurons.
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PMID:Neurochemical characteristics of a novel dorsal root ganglion X neuroblastoma hybrid cell line, F-11. 243 52

The effects of a range of neuropeptides were investigated on the membrane potential of the Schwann cells of the giant nerve fibre of the tropical squid. Vasoactive intestinal peptide (VIP) produced a dose-dependent, long-lasting hyperpolarization of the Schwann-cell membrane potential. Among peptides structurally related to VIP, similar effects were produced by peptide histidine isoleucine (PHI) but not by secretin and glucagon. Substance P and somatostatin also hyperpolarized the Schwann-cell membrane potential but via receptor systems distinct from those activated by VIP. Methionine enkephalin ([Met]-enkephalin) blocked the actions of all the above peptides as well as the effects of DL-octopamine and carbachol. The actions of [Met]-enkephalin upon the VIP responses were antagonized by naloxone. VIP produces its effects on the Schwann-cell membrane potential via a receptor system that is independent from those described previously which mediate the effects of carbachol and DL-octopamine. However, VIP can potentiate the effects of the latter systems. The actions of VIP on the Schwann cell are unlikely to be mediated via changes in adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels and are insensitive to changes in the level of extracellular calcium in the superfusate. The actions of VIP are, however, potentiated in the presence of low concentrations of lithium ions suggesting that the VIP receptor may mediate its effects by inducing the hydrolysis of polyphosphatidylinositols in the Schwann-cell membrane. Evidence is presented for the existence of an endogenous VIP-like component in the normal hyperpolarizing action of giant-axon activity on the membrane potential of the Schwann cell.
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PMID:Peptidergic modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre. 243 97

The effects of injecting ATP, ADP, AMP, adenosine and adenine intrathecally on the pain response induced by the injection of substance P (10 ng/mouse) intrathecally were studied. All the compounds except adenine inhibited the pain response in a dose-related manner. The ED50 values of ATP, ADP, AMP and adenosine were 2.10, 0.93, 0.88 and 0.48 micrograms/mouse, respectively. Pretreatment with theophylline at a dose of 100 mg/kg p.o. markedly diminished all the antinociceptive effects. The effect of adenosine was not affected by s.c. injection of naloxone. These results suggest the existence of adenosine receptors which modulate spinal nociceptive sensory processing, independently of the endogenous opiate system.
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PMID:Spinal antinociceptive effects of adenosine compounds in mice. 244 Jul 5

The localization and distribution of catecholamines, selected neuropeptides, and the cyclic nucleotide second messengers has been determined in the superior cervical ganglion of the stroke-prone variant of the spontaneously hypertensive rat (SHR) and its normotensive Wistar-kyoto (WKY) control. Significant alteration in the frequency of occurrence of dopaminergic small intensely fluorescent cell clusters was seen in the stroke-prone variant of the SHR. The immunofluorescent localization of cyclic AMP (cAMP) and cyclic GMP (cGMP) were also changed in the stroke-prone variant, as was the immunofluorescent staining quantity of the neuropeptides somatostatin and substance P. The morphological pattern of staining for the various compounds in the normotensive control (WKY) was equivalent to the Sprague-Dawley rat strain. The implications of the altered neurochemistry in the superior cervical ganglion on the high blood pressure, and the predisposition for stroke in this strain are discussed.
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PMID:Neurochemical differences in the superior cervical ganglion of the spontaneously hypertensive rat stroke-prone variant. 244 7

Nodose (inferior vagal sensory) ganglia were removed from neonatal rats, enzymatically dispersed using neutral protease, and maintained on previously dispersed rat atriacytes. After 7-10 days in culture, calcitonin gene-related peptide (CGRP) was present in 1-3 times the molar amount of substance P (SP). The content of SP was doubled by the addition of nerve growth factor (NGF) whereas CGRP was significantly less increased by 50% or less. The addition of forskolin increased SP and CGRP levels in cultures with or without NGF by 60-80 percent. Phorbol ester (PMA) did not alter SP content but significantly raised CGRP content by 40% in NGF supplemented cultures (P less than 0.001). Corticosterone, 0.01-0.1 microM, reduced SP content by 30% independently of NGF but had no effect on CGRP. These studies demonstrate that SP in vagal sensory neurons is more sensitive than CGRP to the effects of NGF or corticosterone. Both peptides are up-regulated by presumed increases in intracellular cyclic AMP, while CGRP (or CGRP neurons) may be independently regulated by protein kinase C.
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PMID:Differential regulation of calcitonin gene-related peptide and substance P in cultured neonatal rat vagal sensory neurons. 246 32

1. Intracellular recordings were made from submucous neurones of the guinea-pig caecum. In most experiments, membrane currents were measured using a single-electrode voltage clamp. 2. A potassium current dependent on calcium influx occurred at rest (approximately equal to 200 pA at -60 mV). The amplitude of the current was increased up to 1 nA at -35 mV and decreased to zero at -100 mV; when fully activated the current did not show any inactivation. An inward calcium current, of 15-25 pA in amplitude near -60 mV and insensitive to omega-conotoxin (0.5 microM), probably activated the potassium current. 3. Step depolarizations from potentials negative to -80 mV evoked a transient (less than or equal to 200 ms at -40 mV) potassium current which was blocked by 4-aminopyridine (1-3 mM). Hyperpolarizing commands to potentials negative to -87 mV evoked an inwardly rectifying potassium current which was selectively blocked by caesium (1-2 mM). The residual cell current between -100 and -40 mV in calcium-free solution containing tetraethylammonium (20 mM), caesium (2 mM) and 4-amino-pyridine (3 mM) conformed to constant field assumptions. This current was called a background potassium current. 4. Decrease in membrane conductance during the slow excitatory postsynaptic current (EPSC) was due predominantly (greater than or equal to 90%) to a reduction in the calcium-activated potassium current at -35 mV, but due almost exclusively to a reduction in the background potassium current at potentials more negative than -100 mV. The relative contribution of the two currents to the slow EPSC was entirely dependent on the relative contribution of the currents to the membrane conductance at given potentials. 5. The transient potassium current was unaffected or slightly enhanced during the slow EPSC. The inwardly rectifying potassium current was unaffected during the slow EPSC. 6. Three tachykinins (substance P, substance K and neurokinin B; 3-800 nM), forskolin (1-30 microM), 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo cyclic AMP; 1-3 mM), 3-isobutyl-1-methylxanthine (0.3-1 mM) mimicked the conductance changes during the slow EPSC in a concentration-dependent manner. 7. It is concluded that the slow excitatory synaptic potential in the submucous plexus, presumably mediated by peptidergic transmitters, results from an inactivation of two distinct potassium currents, at least one of which is controlled by intracellular calcium ions.
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PMID:Potassium currents in submucous neurones of guinea-pig caecum and their synaptic modification. 248 32

A peptide derived from fibrinogen degraded by leukocyte elastase, and corresponding to amino acids 30-43 in the B beta-chain of fibrinogen, was evaluated concerning its effects on isolated bovine mesenteric arteries. This peptide induced dilation of the arteries and an increase in both cyclic AMP and cyclic GMP in the vessels. In addition there was an increase in 6-keto-PGF1 alpha indicating an increased release of prostacyclin. The increase in cyclic nucleotides and 6-keto-PGF1 alpha was inhibited by indomethacin, as was the vasodilation. The increase in cyclic GMP was much larger than the increase in cyclic AMP. The effects of the studied peptide are similar to the effects of other vasoactive peptides with a similar structure, such as bradykinin, neurotensin and substance P. The increase in cyclic AMP is probably caused by prostacyclin, a probable mediator of vasodilation. In addition, in certain species vasodilation may be caused by an increase in cyclic GMP.
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PMID:Effect of a peptide derived from fibrinogen degraded by leukocyte elastase on isolated bovine mesenteric arteries. 254 16


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