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)

Substance P (SP) was applied by superfusion (0.8 to 3.4 x 10(-6) M) to neurons of the dorsal motor nucleus of the vagus (DMV) in slice preparations of the rat medulla oblongata. Intracellular recordings showed that 18 of 43 (42%) neurons were depolarized and the depolarization was associated with an increase in membrane input resistance; five of 43 (12%) neurons were hyperpolarized and the hyperpolarization was associated with a decrease in membrane input resistance. Both effects were reversible and persisted after blockade of synaptic transmission by Ca2+ free/high Mg2+ solution. These data show that: 1) vagal neurons in the DMV have receptors for SP; 2) SP may modulate vagal output specially by increasing neuronal excitability; 3) although electrophysiological effects of SP have been studied in a variety of central and peripheral neurons, this is the first evidence of SP effects on DMV; 4) DMV is a particular brain target site in which SP may induce depo- or hyperpolarization.
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PMID:Substance P effects on the dorsal motor nucleus of the vagus. 247 63

The participation of excitatory amino acid (EAA) receptors in the responses of deep dorsal horn neurons to repetitive stimulation of dorsal roots was investigated using a spinal slice preparation and current-clamp and voltage-clamp techniques. Using EAA receptor and substance P (SP) receptor antagonists and current-clamp, slow excitatory synaptic response evoked by 10-20 Hz stimulation consisted of two depolarizing components: an initial component lasting 1-5 s and a late-one of 1-3 min duration. The initial and late components of the slow excitatory postsynaptic currents (EPSCs) can also be distinguished on the basis of their voltage-dependence and sensitivity to Mg2+ ions, D-2-amino-5-phosphonovalerate (D-APV) and 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX). In the presence of Mg2+, the initial component of the slow EPSC increased with membrane hyperpolarization, whereas the late component decreased. In a zero-Mg2+ medium, the initial component was potentiated, but the late component was reduced, or unchanged. CNQX reduced the initial component. In a zero-Mg2+ solution, or at membrane potentials positive to -55 mV in 1 mM Mg2+, D-APV reduced or even abolished the initial component, whereas the late component was not modified by D-APV. We propose that slow excitatory synaptic response evoked in deep dorsal horn neurons by repetitive stimulation of primary afferents has two components, an initial transient component that requires activation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and a late longer-lasting peptidergic component that has been already described (Brain Res., 290 (1984) 336-341.
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PMID:Participation of excitatory amino acid receptors in the slow excitatory synaptic transmission in the rat spinal dorsal horn in vitro. 257 67

[3H]Physalaemin [( 3H]PHY) binds to a single class of noninteracting sites on rat submaxillary gland membranes suspended in high ionic strength media with a KD of 2.7 nM, a Bmax of 240 fmol/mg of protein, and low nonspecific binding. The relative potencies of substance P (SP) and its fragments in competing with [3H]PHY correlate with their relative salivation potencies. This indicates that [3H]PHY interacts with a physiologically relevant SP receptor. In low ionic strength media, the KD of [3H]PHY does not change, but SP and some of its fragments are more potent than PHY in competing with [3H] PHY. Computer-assisted analysis of [3H]PHY and [3H]SP binding in high and low ionic strength media demonstrated that both peptides are equipotent in high ionic strength but that the affinity of SP increases by 70-fold in low ionic strength. The SP fragments that contain a basic residue in positions 1 and/or 3 also display an increased affinity in low ionic strength. These findings document that [3H]PHY binding in high ionic strength (mu = 0.6) accurately reflects the pharmacological potencies of agonists on the SP-P receptor. The binding of [3H]PHY, like that of [3H]SP, increases by the addition of divalent cations (Mg2+ greater than Ca2+ greater than Mn2+). Guanine nucleotides decrease [3H]PHY binding by decreasing the Bmax to the same level (160 fmol/mg of protein), in the presence or absence of Mg2+.
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PMID:Specific binding of [3H-Tyr8]physalaemin to rat submaxillary gland substance P receptor. 257 11

Vincamine in low concentrations induced a sustained contraction of the isolated guinea pig trachealis with long latency and slow onset and, in high concentrations, it induced relaxation which was potentiated in the precontracted trachealis. Vinpocetine had actions similar to those of vincamine on trachealis, however its relaxant effect was more pronounced. The vincamine-induced trachealis contraction was not changed by substance P desensitization, was reduced by tetrodotoxin, nifedipine and low Ca2+ high Mg2+ solution and increased in nominally Ca2+-free solution. The vincamine-induced relaxation of precontracted trachealis was increased by guanethidine and was not affected by propranolol, high Mg2+-low Ca2+ solution and tetrodotoxin. Vincamine- and vinpocetine-induced trachealis contraction as well as vinpocetine-induced relaxation at basal tension were abolished by indomethacin. Vincamine in a low concentration shifted to the left the concentration-effect curve for CaCl2 in the K+-depolarized trachealis, and shifted it to the right at a high concentration. Our results indicate that the contractile and relaxant actions of vincamine and vinpocetine on the guinea pig trachealis may be due to the generation of prostaglandins and to changes in the membrane Ca2+ fluxes and/or the intracellular Ca2+ distribution.
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PMID:Trachealis responses induced by vincamine and vinpocetine; inhibition by indomethacin and Ca2+ dependence. 274 76

The effect of 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) on the isolated spinal cord of the immature rat was examined using extracellular recording. At concentrations less than 20 microM CHEB increased the monosynaptic reflex (MSR) but depressed the reflex at greater concentrations (30-100 microM). At concentrations which enhanced the monosynaptic reflex, CHEB reduced the responses of motoneurones to glycine and to a lesser extent to those of L-glutamate. In the presence of strychnine (5 microM), which enhanced both mono- and polysynaptic reflexes, CHEB produced only slight enhancement of the monosynaptic reflex. At concentrations of 30-100 microM the responses to gamma-aminobutyric acid (GABA), glycine, L-glutamate and eledoisin-related peptide (ERP a substance P and analogue) were all reduced. At these concentrations CHEB directly depolarised the motoneurone membrane. Increases in [Mg2+]0, which reduced spontaneous activity, blocked the enhancement, by CHEB, of the monosynaptic reflex. The actions of CHEB in small doses may be due therefore to its ability to block the action of glycine and thus block tonic inhibition.
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PMID:Strychnine-like action of the convulsant barbiturate, CHEB. 286

Mg participates in immune responses in numerous ways: as a cofactor for immunoglobulin synthesis, C'3 convertase, immune cell adherence, antibody-dependent cytolysis, IgM lymphocyte binding, macrophage response to lymphokines, T helper-B cell adherence, binding of substance P to lymphoblasts and antigen binding to macrophage RNA. Mg deficiency in rodents impairs IgG synthesis and cell-mediated immunity; complications include thymus atrophy, elevated IgE, hypereosinophilia, histaminosis and lymphoma. Immunologic sequelae of Mg deficiency in humans are subtle and may be affected by genetic control of blood cell Mg concentration. Abnormal C' activation, excess antibody production and susceptibility to allergy and to chronic fungal and viral infections have been reported. Mg appears to play a protective role in acute allergic reactions.
Magnesium 1988
PMID:Magnesium and immune function: an overview. 307 45

Some biochemical factors of the iris-ciliary body of the rabbit have been examined for effects induced by water-soluble marihuana-derived material (MDM). Adenylate cyclase activity and sensitivity to beta-adrenergic agonists were unchanged, as measured 4 hours after MDM administration in vivo. Magnesium-dependent and anion-sensitive, but not sodium-potassium, ATPase activities were inhibited 6 hours after MDM administration in vivo, although they were unaffected by in vitro incubation. Topical administration of a potent substance P antagonist had no effect on the time course or magnitude of intravenous MDM-induced ocular effects in rabbit. Intravenously administered sugars antagonized the effects of MDM on intraocular pressure. A variety of drugs which display a range of biochemical effects varying from beta-adrenergic receptor agonism, to alteration of glycoprotein residues were employed. None of the agents employed, ranging from cAMP modifiers to protein synthesis blockers, had any effect on the MDM-induced response. It is apparent that the mechanism underlying the ocular hypotensive effect of MDM does not reside in mediation through adenylate cyclase, ATPase or substance P, but rather through a mechanism mediated by terminal sugar moieties on the molecule. The data suggest that modification of the surface membrane glycoprotein residues on the ciliary epithelium can induce marked alterations in aqueous humor flow rate.
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PMID:Marihuana-derived material: biochemical studies of the ocular responses. 316 May 44

The neuropeptide substance P (SP), which has been demonstrated to bind specifically to human blood T lymphocytes and to stimulate their uptake of [3H]thymidine and [3H]leucine, now is shown to bind stereospecifically to cultured human lymphoblasts of the IM-9 line. The specific binding of [3H]SP by IM-9 lymphoblasts increases linearly with the concentration of IM-9 lymphoblasts, achieves a plateau after approximately 15 to 20 min at 4 degrees C and 4 to 6 min at 37 degrees C, and is rapidly reversible at both 4 degrees C and 37 degrees C. The binding of [3H]SP at steady-state conditions demonstrates a dissociation constant (KD) of 0.65 +/- 0.19 nM (mean +/- SD, n = 5) and 22,641 +/- 6143 receptors per IM-9 lymphoblast. Maximal specific binding of [3H]SP to IM-9 lymphoblasts is observed at pH 7.4 and is dependent on the presence of Mg2+, but not Ca2+, in the medium. The peptide structural determinants of the inhibition of binding of [3H]SP to IM-9 lymphoblasts by substituent peptides and homologs of SP indicate that the receptors recognize predominantly the carboxy-terminal portion of SP. The characteristics of the interaction of SP with IM-9 lymphoblasts suggests a receptor-directed mechanism by which neuropeptides may modulate specifically the contributions of lymphocytes to immunity.
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PMID:Stereospecific receptors for substance P on cultured human IM-9 lymphoblasts. 609 69

1. Binding of 125I-Tyr8-substance P (SP) to synaptic vesicles shows an uneven distribution within the brain and the spinal cord. The regional distribution has a positive correlation with the SP-content, except in the hypothalamus. 2. Ca2+ and MG2+-ions (1 and 10 mM) decrease the number of binding sites without alteration of affinity. EDTA and EGTA enhance SP-binding which is interpreted as being due to removal of the inhibitory influence of endogenous Ca2+ and Mg2+ through chelation with these agents. No significant inhibition of SP binding was observed by Na+ or K+ in concentrations below 100 mM. 3. Pretreatment of synaptic vesicles with trypsin or with phospholipase A2, C and D leads to a total loss of SP binding showing a proteolipid or a joint protein-phospholipid nature of these binding sites. SH groups do not contribute to SP binding since no effect of N-ethylmaleimide and monoidoacetic acid on SP binding was found.
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PMID:Regional distribution and biochemical properties of 125I-Tyr8-substance P binding sites in synaptic vesicles. 615 17

Effects of substance P on neurons of the guinea-pig hypothalamus in vitro and antagonism between substance P and baclofen were investigated. Substance P increased the firing rate of neurons in the medium containing 0 mM Ca2+ and 12 mM Mg2+. The excitatory action of substance P was antagonized by a low dose of baclofen whereas that of acetylcholine was not antagonized even by much higher doses of baclofen.
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PMID:Further support for the postsynaptic action of substance P and its blockade with baclofen in neurons of the guinea-pig hypothalamus in vitro. 616 89


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