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) and its COOH-terminal fragment (6-11) were coupled to bovine serum albumin by glutaraldehyde and used to elicit antibodies. Anti-SP and anti-SP6-11 antibodies bound to the same extent 125I-[Tyr8]-SP and 125I-[T-Lys6]-SP6-11. The latter was obtained after conjugation of the [Lys6]-SP6-11 with cold Bolton-Hunter reagent and then labelling by the chloramine-T method. In contrast to 125I-[Tyr8]-SP, 125I-[Tyr8]-SP6-11 was poorly bound by both anti-SP and anti-SP6-11 antibodies. Synthetic fragments of SP shorter than SP7-11 did not react with anti-SP6-11 antibodies. It is concluded that the antigenic determinant is within the COOH-terminal pentapeptide, and that Phe7, Phe8, Leu10 and Met11 contribute significantly to both anti-SP and anti-SP6-11 immunoreactivity.
Mol Immunol 1984 Aug
PMID:Immunogenic and antigenic properties of the COOH-terminal hexapeptide of substance P. 620 58

Using the indirect immunofluorescence technique of Coons and collaborates, somatostatin-like immunoreactivity was found in skin lesions of patients presented with urticaria pigmentosa. The cytoplasmic immunoreactivity was sometimes of a granular type. In addition, immunofluorescence was also observed in certain surrounding connective tissue elements. No specific staining was seen when supplementing the first antiserum with control serum, nor could any unique specific immunofluorescence by found in the pathological areas (compared with skin of normal healthy volunteers) after incubation with antibodies to substance P, vasoactive intestinal polypeptide or avian pancreatic polypeptide. No thyrotropin releasing hormone or enkephalin immunoreactivity was seen in skin from either the patients or the controls.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Immunohistochemical localization of somatostatin-like immunoreactivity in skin lesions from patients with urticaria pigmentosa. 620 41

A new ligand for investigating tachykinin-binding site subtypes was synthesized by coupling the 125I-Bolton and Hunter reagent to eledoisin (125I-BHE). Using a synaptosomal preparation (P2 fraction) of rat cerebral cortex, 125I-BHE was shown to bind with apparent high affinity (apparent Kd = 15.3 nM). When concentrations of up to 30 nM 125I-BHE were used, 125I-BHE binding was specific, saturable, reversible, and temperature-dependent. In contrast to [3H]dopamine, 125I-BHE was not taken up within synaptosomes by an ouabain-sensitive process. Eledoisin, kassinin, and substance P were examined for their ability to inhibit specific 125I-BHE binding to cortical synaptosomes. Eledoisin and kassinin were considerably more potent than substance P, in contrast to the order of potency observed for specific 125I-Bolton-Hunter substance P (125I-BHSP) binding. Specific 125I-BHE binding was highest in the cerebral cortex and hypothalamus; intermediate in the hippocampus, striatum, and thalamus; low in the mesencephalon, septum, and substantia nigra; and absent in the cerebellum. Comparison of these data with those previously obtained for 125I-BHSP binding to synaptosomes indicated that 125I-BHE-labeled binding sites differ markedly from those of 125I-BHSP-labeled binding sites. Therefore, tachykinin receptors other than substance P receptors seem to be present in the central nervous system.
Mol Pharmacol 1984 Sep
PMID:A new type of tachykinin binding site in the rat brain characterized by specific binding of a labeled eledoisin derivative. 620 21

Tuftsin, a natural occurring tetrapeptide, has been found to exhibit several biological activities connected with immune system function. Although little is known about tuftsin's 'biogenesis', much information has been gleaned about its structure-function relationships, which have shown that several features of the molecule are essential for expression of full biological activity. Furthermore, specific receptor sites for tuftsin have been found to exist exclusively on phagocytic cells. Research indicates that tuftsin binding to target cells effect intracellular calcium and cyclic nucleotide levels. Implication of these facts on tuftsin's mode of action are discussed. Basic peptidic segments resembling tuftsin are found in a variety of regulatory peptides. Questions are, therefore, raised as to the biospecificity an cross-reactivity of these sequences. Substance P, one such peptide, which binds with and activates tuftsin receptors, is described. In light of tuftsin's therapeutic potential, assays for its determination have been introduced. When applied to analyze human blood serum of normal as well as of various pathological origins, direct correlation was found between tuftsin levels and susceptibility to bacterial infections.
Mol Cell Biochem 1981 Dec 04
PMID:Tuftsin, Thr-Lys-Pro-Arg. Anatomy of an immunologically active peptide. 703 69

Two classes of structurally different tachykinin neurokinin3 (NK3) antagonists were used to evaluate species difference in antagonist binding between human and rat NK3 receptors. In competition binding experiments with [125I-MePhe7]NKB as radioligand, PD 154740, PD 157672, SR 48968, and SR 142801 displayed lower Ki values for the human NK3 receptor (40 +/- 4, 12 +/- 1,350 +/- 50, and 0.40 +/- 0.05 nM, respectively) than for the rat NK3 receptor (2450 +/- 130, 288 +/- 25, > 10,000, and 11.0 +/- 0.5 nM, respectively). Data from in vitro functional assay showed similar species preference as observed with the competition binding assay. It was shown previously that substitution of only two amino acid residues in the rat receptor to their human counterparts could change the species selectivity of SR 48968, a weak NK3 antagonist. In the double-substituted rat mutant, all three antagonists (PD 154740, PD 157672, and SR 142801) displayed Ki values (76 +/- 8, 16 +/- 2, and 0.50 +/- 0.05 nM, respectively) very similar to the Ki values for the wild-type human NK3 receptor. Thus, in addition to their previously reported effects on SR 48968, these two amino acid residues are responsible for the species selectivity of these three additional NK3 antagonists. Because PD 154740 and PD 157672 are very different structurally from SR 48968 and SR 142801, our results indicate that the two identified residues may be involved in adopting a receptor conformation that favors the binding of NK3 antagonists that display species preference for the human NK3 receptor.
Mol Pharmacol 1995 Oct
PMID:Two classes of structurally different antagonists display similar species preference for the human tachykinin neurokinin3 receptor. 747 98

The mRNA levels encoding neuropeptides were measured in the caudate nucleus, putamen and nucleus accumbens of common marmosets exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine pyridine (MPTP). Motor deficits induced by MPTP treatment were characterized by akinesia, postural abnormalities and rigidity. Seven days after MPTP treatment, there was a marked increase in levels of enkephalin mRNA in the caudate nucleus and putamen. In contrast, the hybridization signal for substance P mRNA was reduced. Alterations in the mRNA encoding neuropeptides were similar but less extensive in marmosets at 18-50 months following MPTP treatment. No significant changes in enkephalin or substance P mRNA in the nucleus accumbens were observed at either time. Treatment with L-DOPA plus carbidopa for 4 weeks reversed MPTP-induce motor deficits and other behavioural abnormalities. The decrease in substance P mRNA in the striatum of MPTP-treated animals was reversed by L-DOPA treatment and reached levels above those found in normal animals. In contrast, the increase in enkephalin mRNA in marmosets treated with MPTP was not altered by L-DOPA treatment. In the nucleus accumbens the levels of peptide mRNA were not affected by L-DOPA treatment. Loss of nigral dopamine cells in a primate species causes opposing alterations in the expression of enkephalin and substance P mRNA in the caudate nucleus and putamen. No changes were observed in the nucleus accumbens, which reflects the resistance of the mesolimbic neurons to MPTP toxicity. While the decrease in substance P mRNA was reversed by L-DOPA treatment, the increase in enkephalin mRNA was not. This may partly indicate the greater effect of L-DOPA on the direct GABA pathway compared to the indirect output pathway from the striatum.
Brain Res Mol Brain Res 1995 Sep
PMID:L-DOPA reverses altered gene expression of substance P but not enkephalin in the caudate-putamen of common marmosets treated with MPTP. 750 Aug 41

In the gracile axonal dystrophy (GAD) mutant mouse, the dying-back type axonal dystrophy of the primary afferent neurons in the gracile tract of the spinal cord was marked by severe gliosis characterized by the hypertrophy and proliferation of the fibrous astrocytes. Immunocytochemical observation for substance P (SP) revealed that SP-positive cells increased in the lesioned sites, primarily in the gracile nucleus of the medulla and subsequently in the gracile fasciculus of the spinal cord. The combined immunostaining of both SP and glial fibrillary acidic protein (GFAP) indicated that a strong correspondence exists between GFAP-positive networks and SP-positive grains, suggesting that SP was accumulated in the cytoplasm of astrocytes. The networks of SP-positive astrocytes spread all over the gracile tract and were densest at the subpial membrane. Similar lesions and SP activity were detected along the marginal zone of the lateral and ventral funiculi. Using an electron microscope, in addition to SP-positive axonal terminals in the gracile nucleus, most SP-positive cells in the gracile tract were identified as reactive astrocytes whose processes surrounded myelinated and nonmyelinated axons, and extended their foot processes to the blood vessels. By in situ hybridization histochemistry of SP mRNA, we confirmed the synthesis of SP in the astrocytes. Although the functional significance of SP within astrocytes is not established here, these results imply that the astrocytes may play a role as a gliotransmitter through which the progress of axonal degeneration in the spinal cord was modified.
Mol Chem Neuropathol 1993 Sep
PMID:Substance P-immunoreactive astrocytes in gracile sensory nervous tract of spinal cord in gracile axonal dystrophy mutant mouse. 750 92

The binding of [3H]substance P to nicotinic acetylcholine receptor-enriched Torpedo electroplaque membranes was characterized. In the absence of cholinergic agonist, [3H]substance P binding was displaced by unlabeled substance P with an IC50 of 31 +/- 7 microM. In the presence of 10 mM carbamylcholine, displacement reflected two populations of binding sites with IC50 values of 0.93 +/- 0.39 and 30 +/- 5 microM, with the higher affinity component contributing 69 +/- 2% of the inhibition. Equilibrium binding parameters were calculated by transformation of the concentration dependences of inhibition into saturation isotherms. In the absence of agonist, substance P bound with a Kd of 42 +/- 7 microM to 3-4 sites/alpha-bungarotoxin binding site. In the presence of agonist, substance P bound to two sites, a low affinity site not significantly different from that seen in the absence of agonist (Kd = 25 +/- 8 microM, approximately 3 sites/alpha-bungarotoxin site) and a high affinity site with a Kd of 0.55 +/- 0.32 microM (approximately 1 site/2 alpha-bungarotoxin sites, 1 site/receptor). The increase in substance P binding induced by carbamylcholine was blocked by the nicotinic antagonists alpha-bungarotoxin and d-tubocurarine but was not affected by the muscarinic antagonist atropine. The concentration dependence of the carbamylcholine-induced increase had two components, with EC50 values for the agonist of 9.1 +/- 4.2 microM (56 +/- 16% of the increase) and 1.3 +/- 0.5 mM. The structural specificity of agonist-dependent high affinity substance P binding was identical to that seen for inhibition of nicotinic receptor activation and substantially different from that of binding to the G protein-coupled tachykinin receptors. From the time courses of association, it appears that substance P binds preferentially to a transient agonist-induced receptor state. The gamma and delta subunits of the receptor were specifically labeled in an agonist-dependent manner after cross-linking of [3H]substance P to the receptor with the bifunctional cross-linking reagent bis[2-(succinimidooxycarbonyloxy)ethyl]sulfone or after photoaffinity labeling of the receptor with 125I-p-benzoylphenylalanine-substance P. These results demonstrate the existence of a high affinity agonist-induced binding site for substance P on the nicotinic acetylcholine receptor that probably mediates the noncompetitive inhibition by the peptide of receptor activation.
Mol Pharmacol 1994 Feb
PMID:Characterization of the binding of [3H]substance P to the nicotinic acetylcholine receptor of Torpedo electroplaque. 750 39

The hexapeptide [pGlu6,Pro9]substance P (SP)6-11, septide, has been shown to be an agonist as potent as SP in eliciting smooth muscle contraction in several in vitro preparations, while being a poor competitor of labeled SP binding. These results, as well as other pharmacological data, have suggested the existence of either a specific septide receptor or a septide site on the neurokinin (NK)1 receptor distinct from that for SP. We have used rat recombinant NK1 receptor expressed in COS-1 cells to address this issue. Both functional (agonist-induced inositol phosphate accumulation) and radioligand binding studies were conducted on transiently transfected cells. SP and septide elicited similar maximal increases (4-6-fold) in inositol phosphate levels in transfected cells, with EC50 values of 0.05 +/- 0.02 nM for SP and 5 +/- 2 nM for septide. No additivity of the maximal responses to the two agonists was observed, and neither agonist evoked any response in sham-transfected cells. RP 67580 was a competitive inhibitor of SP responses, with an inhibition constant (KB) of 13 +/- 2 nM, in agreement with displacement studies of [3H]SP binding to membranes and intact transfected cells (Ki values of 10 +/- 4 nM, and 1.16 +/- 0.06 nM, respectively). In comparison, septide responses were inhibited by RP 67580 in an uncompetitive fashion, with an apparent KB* value of 1.5 +/- 0.2 nM. Septide was a weak competitor of [3H]SP binding, with dissociation constants (Ki) of 2.9 +/- 0.6 microM and 3.7 +/- 0.9 microM for membranes and intact transfected cells, respectively. Similarly, septide at concentrations up to 10 microM did not affect [3H]RP 67580 binding. In conclusion, we have demonstrated that septide is a potent functional agonist of the NK1 receptor but it seems to act at a specific subsite different from that for SP. Although not ruling out the existence of selective septide receptors in some tissues, these results could explain some of the discrepancies with regard to the pharmacological properties of septide. Furthermore, a specific septide site on the NK1 receptor could represent an original pharmacological target.
Mol Pharmacol 1994 Feb
PMID:Septide: an agonist for the NK1 receptor acting at a site distinct from substance P. 750 40

During evolution mutations have occurred in peptide receptors that are neutral with respect to binding of the natural peptide ligand but frequently affect the binding of nonpeptide antagonists. By systematically introducing the nonconserved residues from the human neurokinin (NK)-1 receptor into the corresponding rat receptor we have attempted to localize the structural elements that are responsible for 15-76-fold higher affinity of three tachykinin nonpeptide antagonists for the human receptor, compared with the corresponding rat receptor. Surprisingly, exchange of the four divergent residues located around the previously located apparent binding site for CP 96,345 and FK 888 at the top of transmembrane segment (TM) V and VI, either alone or as a group, did not affect the binding of these nonpeptide compounds. However, substitution of Ser290 in TM VII of the rat receptor with isoleucine present in the human receptor increased the affinity for FK 888 20-fold and that for CP 96345 6-fold, corresponding to an affinity that was only about 4-fold less than the affinity for the human NK-1 receptor. Full human-like affinity for FK 888 and CP 96,345 could be conveyed to the rat receptor by the combined substitution of Ser290 in TM VII to isoleucine and Leu116 in TM III to valine. The NK-2 receptor-selective compound SR 48,968 was found to bind with low affinity to the human NK-1 receptor but with 15-fold even lower affinity to the rat receptor. Substitution of residue 290, which is situated within the previously located binding site for this compound, could completely account for this difference. These data demonstrate that the species selectivities of the nonpeptide antagonists CP 96345, FK 888, and SR 48,968, independently of clear differences in their chemical structures and modes of discovery, have a similar structural basis, being dependent on two divergent residues that apparently are not involved in peptide agonist binding.
Mol Pharmacol 1994 Feb
PMID:The species selectivity of chemically distinct tachykinin nonpeptide antagonists is dependent on common divergent residues of the rat and human neurokinin-1 receptors. 750 41


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