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)

Responses of dorsal horn neurons to iontophoretic application of substance P (80-120 nA), and to noxious thermal and noxious mechanical stimulations of the receptive field in the hind limb were tested in adult cats before and after the administration of the specific, non-peptide, NK-1 receptor antagonist CP-96,345 (0.5 mg/kg, i.v.). CP-96,345 inhibited the response of the neurones to substance P and also the response of these substance P-sensitive neurones to noxious thermal stimulation. The response of the substance P-insensitive neurones to noxious heat stimulations were, however, unaffected by CP-96,345. The effect of CP-96,345 on the response of neurones to noxious mechanical stimulation was variable. The results confirm the role of substance P in thermal nociception.
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PMID:Novel substance P antagonist, CP-96,345, blocks responses of cat spinal dorsal horn neurons to noxious cutaneous stimulation and to substance P. 172 68

Responses of gastric myenteric neurones evoked by the mammalian tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were investigated using conventional intracellular recording methods. Application of the tachykinins caused a long lasting depolarization of the membrane potential which was associated with increased spike discharge and augmented excitability of the cells. The responses slowly desensitized. Additionally, cross desensitization occurred between SP, NKA and NKB. Both the NK-1 receptor agonist [Sar9,MetO2(11)]SP and the NK-2 receptor agonist [beta-Ala8]NKA(4-10) had no effect on the electrical properties of the neurones. Only the NK-3 receptor agonist [MePhe7]NKB mimicked the excitatory response observed during SP, NKA and NKB applications. [MePhe7]NKB-induced desensitization abolished the response to SP, NKA and NKB. However, long lasting applications of [Sar9,MetO2(11)]SP or [beta-Ala8]NKA(4-10) had no effect on the SP, NKA or NKB responses. The excitatory effect of SP, NKA and NKB remained unchanged during application of the tachykinin analogues [D-Arg1,D-Trp7,9,Leu11]SP and [Tyr5,D-Trp6,8,9,Arg10]NKA(4-10). The results indicate that SP, NKA and NKB act as excitatory neuromodulators within the enteric nervous system of the stomach. The effects of SP, NKA and NKB appeared to be mediated by activation of NK-3 receptors.
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PMID:Effects of tachykinins on myenteric neurones of the guinea-pig gastric corpus: involvement of NK-3 receptors. 172 75

A series of mouse hybridomas that produced monoclonal antibodies reactive with Substance P was prepared in an attempt to find a surrogate NK-1 receptor. When the binding profile of one particular antibody, SubP14.36.1, was compared in a rank order plot with NK-1 receptors against various agonists and antagonists of Substance P, a high correlation was found between these two binding structures. In addition, this monoclonal antibody inhibited a functional assay for Substance P. This result indicated that the pharmacological effects of this peptide can be blocked by an antibody (Ab).
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PMID:Preparation and characterization of monoclonal antibodies to substance P. 172 60

Two new cyclic analogues of physalaemin were designed on the basis of the conformation found in DMSO solution. Glp-Ala-cyclo(-Asp-Pro-Asn-Lys-)-Phe-Tyr-Gly-Leu-Met-NH2 (1) was synthesized by cyclization of physalaemin. In 2 the Asp residue was replaced by Glu. The linear analogue of 2 was synthesized by the solid phase method and subsequently cyclized. Two-dimensional nmr methods were employed to assign the proton and carbon resonances. Proton-proton distances were extracted from rotating frame nuclear Overhauser effect spectra and used as restraints in the molecular dynamics calculations. Analogue 1 was found to have a similar conformation as physalaemin, whereas 2 did not form intramolecular hydrogen bonds. The pharmacological evaluation revealed that both peptides have similar potencies as physalaemin in the dog carotid artery (NK-1 receptor). Therefore, the charged side chains of physalaemin appear not essential for NK-1 activation. However, the other tachykinin receptors show good sensitivity to the cyclic peptides. It is concluded that the replacement of a salt bridge by an amide bond connecting the side chains of natural residues might provide useful information about the biological significance of some charged side chains of neurokinins.
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PMID:Conformation-based design of two cyclic physalaemin analogues. 193 67

The tachykinins comprise a family of closely related peptides that participate in the regulation of diverse biological processes. The tachykinin peptides substance P, neurokinin A, neurokinin A(3-10), neuropeptide K, and neuropeptide gamma are produced from a single preprotachykinin gene as a result of differential RNA splicing and differential posttranslational processing. Another tachykinin, neurokinin B, is produced from a separate preprotachykinin gene. These preprotachykinin mRNAs and peptide products are differentially distributed throughout the nervous system. Three distinct G protein-coupled tachykinin receptors exist for these tachykinin peptides. The three receptors interact differentially with the tachykinin peptides and are uniquely distributed throughout the nervous system. The NK-1 receptor preferentially interacts with substance P, the NK-2 receptor prefers neurokinin A, neuropeptide K, and neuropeptide gamma, and the NK-3 receptor interacts best with neurokinin B. Examples of the roles of tachykinin peptidergic neuronal systems are taken from the spinal cord sensory system and the nigrostriatal extrapyramidal motor system. Analysis of the functional significance of multiple tachykinin peptide systems, receptor-second messenger coupling mechanisms, and developmental and regulatory mechanisms underlying peptide mRNA and receptor expression represent areas of current and future investigation.
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PMID:Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors, and regulatory mechanisms. 196 74

Reflex responses evoked by distension of the guinea-pig small intestine were recorded from the circular muscle with intracellular microelectrodes. For this purpose a mechanically stable preparation that allowed the intestinal wall to be distended within 9 mm of the recording site was developed. A segment of intestine was opened along the mesenteric border and pinned mucosa uppermost over a balloon set in the base of an organ bath, so that inflation of the balloon could distend the intestinal wall without simultaneously pushing against the mucosa. Compound excitatory junction potentials (EJPs) and compound inhibitory junction potentials (IJPs) were recorded at sites up to 40 mm oral and anal to the distending stimulus, respectively. The compound EJPs recorded orally had amplitudes of up to 24 mV and declined to baseline during distensions that exceeded 10-15 s. Distensions at intervals of less than 20 s evoked successively smaller oral compound EJPs; after four distensions in 30 the amplitude of the compound EJP had fallen to less than 10%. The amplitude of the oral compound EJP was reduced by hyoscine (1 microM), but the extent of the reduction depended on the degree of distension; responses to mild stimuli were blocked, whereas those to strong stimuli were only slightly reduced. The amplitude of the hyoscine-resistant component of the compound EJP was markedly reduced by antagonists of substance P receptors in the muscle. In the presence of muscarinic and substance P receptor antagonists, a transient compound IJP could be detected on the oral side of the stimulus. The compound IJPs recorded anal to the distension had amplitudes up to 22 mV but the potential returned to baseline during prolonged distension. In the presence of hyoscine (1 microM) some inhibitory activity continued throughout prolonged stimuli. Compound IJP amplitudes were not significantly reduced by repeated distensions separated by more than 6 s. At anal sites a transient depolarization (off-response) was recorded immediately following the termination of a distension in some preparations. The off-response was unaffected by hyoscine and was more readily observed after the further addition of substance P antagonists. The compound IJPs were almost completely blocked by apamin (0.2 microM). The compound EJPs and IJPs recorded orally were blocked by hexamethonium (100 microM), but the amplitudes of compound IJPs recorded anally were significantly reduced by hexamethonium (100-200 microM) only at recording sites greater than 15 mm from the centre of the balloon. The off-response was reduced by hexamethonium at all sites.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Distension-evoked ascending and descending reflexes in the circular muscle of guinea-pig ileum: an intracellular study. 197 Dec 88

Substance P is a member of the tachykinin peptide family and participates in the regulation of diverse biological processes. The polymerase chain reaction and conventional library screening were used to isolate a complementary DNA (cDNA) encoding the rat substance P receptor from brain and submandibular gland. By homology analysis, this receptor belongs to the G protein-coupled receptor superfamily. The receptor cDNA was expressed in a mammalian cell line and the ligand binding properties of the encoded receptor were pharmacologically defined by Scatchard analysis and tachykinin peptide displacement as those of a substance P receptor. The distribution of the messenger RNA for this receptor is highest in urinary bladder, submandibular gland, striatum, and spinal cord, which is consistent with the known distribution of substance P receptor binding sites. Thus, this receptor appears to mediate the primary actions of substance P in various brain regions and peripheral tissues.
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PMID:Molecular characterization of a functional cDNA encoding the rat substance P receptor. 215 52

Infusion of neurotensin, substance P and methionine-enkephalin induces colonic contraction in the cat. The present study was performed to investigate the effect of various pharmacological blocking agents on colonic contraction evoked by these peptides infused by the i.a. or i.v. route. The contractions caused by infusions of neurotensin were blocked by tetrodotoxin (1 micrograms kg-1 i.a.), hexamethionium (10 mg kg-1 i.v.), atropine (0.1 mg kg-1 i.v.) or somatostatin (100 pmol min-1 i.a.), but not by haloperidol, methysergide, mepyramine, cimetidine or naloxone. The contractile effect of substance P on the colon was abolished by the substance P receptor antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-substance P (70 nmol min-1 i.a.). No other blockers used, such as tetrodotoxin, hexamethonium, atropine, mepyramine, cimetidine, methysergide, naloxone or somatostatin inhibited the response to substance P. Methionine-enkephalin produced a colonic contraction that was completely blocked by naloxone (1 mg kg-1 i.a.). Both atropine (0.1 mg kg-1 i.v.) and somatostatin (100 pmol min-1 i.a.) reduced the contractile response. However, tetrodotoxin, hexamethonium, mepyramine, cimetidine and methysergide did not affect the response to methionine-enkephalin. All adrenergic blockers tested, that is, guanethidine, propranolol and phentolamine, increased the contractile responses to the peptides. The results indicate that the colonic contraction induced by neurotensin is mediated via nervous cholinergic pathways. Substance P induces colonic contraction, probably by a direct effect on smooth muscle substance P receptors. Methionine-enkephalin induces colonic contraction which could be blocked by naloxone. However, a cholinergic or peptidergic link may also be involved in the response to methionine-enkephalin.
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PMID:Pharmacological analysis of the mechanism of action for colonic contraction induced by neurotensin, substance P and methionine-enkephalin. 241 19

Spantide ([d-Arg1, d-Trp7,9, Leu11] substance P) was shown to function not only as a substance P receptor antagonist but also as a bombesin receptor antagonist. This study examined the effects of spantide on intravenous bombesin-induced stimulation of gastrin and acid secretion. Dogs were infused with spantide (1 or 10 nmol kg 1 hr 1) or saline and bombesin (60 pmol kg-1 hr-1), and the gastric acid and plasma gastrin responses were monitored. Spantide did not significantly modify gastrin or gastric acid secretion induced by bombesin. It is concluded that spantide may not be a useful bombesin antagonist for in vivo studies.
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PMID:Spantide: failure to antagonize bombesin-induced stimulation of gastrin secretion in dogs. 241 1

The undecapeptide substance P (SP) was tested for its ability to promote human monocyte chemotaxis in a modified Boyden chamber assay. Substance P was found to be active in this assay system with an ED50 for chemotactic effect of approximately 10(-13) M. This response was shown to be chemotactic in nature since a concentration gradient of attractant was required for maximal effect. Other substance P analogs tested showed a rank order of potency of substance P greater than or equal to SP(3-11) greater than SP(8-11) approximately equal to SP(9-11) much greater than SP(1-9), SP, free acid. These results suggest that chemotactic responsiveness is largely encoded in the C-terminus of the molecule. The relative potency order for SP and its analogs in promoting monocyte chemotaxis correlates well with their potencies in displacing labeled SP when binding sites are directly measured in other tissues, such as rat brain or human lymphocytes. Additionally, the chemotactic effects of SP could be partially reversed by the weak antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP. The N-formyl peptide receptor antagonist, t-Boc-Phe-Leu-Phe-Leu-Phe, did not block SP-mediated chemotaxis, further indicating the specificity of these effects. These results suggest the existence of a specific substance P receptor on human monocytes which directs this chemotactic response. The ability of monocytes to respond chemotactically to SP may be relevant to the enhancing effects of SP in arthritis or other inflammatory diseases.
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PMID:Substance P receptor-mediated chemotaxis of human monocytes. 241 6


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