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)

Binding sites for the [125I]Bolton-Hunter labeled substance P (BH.SP) were studied in homogenates of rat brain. Binding at 4 degrees C was much lower than at 25 degree C or 37 degrees C, but degradation of the peptide was very important at 37 degrees C. A mixture of peptidases inhibitors (bacitracin 4 x 10(-5) M), chymostatin (2 x 10(-6) M), leupeptin (4 x 10(-6) M), phosphoramidon (4 x 10(-6) M) was needed to stabilize the binding conditions, which were established as follows: BH.SP 40 pM, membrane preparation 1.25 mg/ml, incubation 20 min, temperature 25 degrees C and pH 7.4, in the presence of peptidase inhibitors. Binding occurred rapidly and was maximum at 20 min: it increased linearly with the amount of membranes added. It was saturable and readily reversible. Kd and receptor concentration were respectively 0.4 +/- 0.2 nM and 17 +/- 1 fmol/mg protein. Kd value measured in kinetic studies (0.2 nM) was similar to the one measured by saturation experiments (0.6 nM). Several analogues, homologues or fragments of SP were shown to inhibit BH.SP binding: their relative affinities were compatible with an interaction on a binding site of the type NK-1. This was confirmed with new selective agonists. [Sar9,Met(O2)11]SP, the NK-1 selective ligand was very potent, while [Nle10]NKA (4-10) (NK-2 selective) and [MePhe7]NKB (NK-3 selective) were nearly inactive. The present results confirm the findings of other similar studies and stress the importance of using (a) peptidase inhibitors for obtaining stable binding conditions and (b) selective agonists for characterizing NK-1 receptor sites in rat brain.
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PMID:Comparison of binding assay and biological activity on a NK-1 system with new selective agonists. 248 52

1. Tachykinin immunoreactivity has been quantified and chemically characterised in extracts of the monogenean parasite, Diclidophora merlangi and its fish host, Merlangius merlangus, by means of four tachykinin radioimmunoassays interfaced with gel permeation chromatography and reverse-phase HPLC. 2. Of the two tachykinins identified in parasite tissue, one was SP-like and the other was NKA-like, although neither was identical to previously identified tachykinins. 3. Three tachykinins were identified in extracts of whiting GI tract, one of which was a neuropeptide and also occurred in whiting brain. 4. The parasite and fish tachykinins had different molecular weights and elution profiles in HPLC analyses, and were therefore chemically distinct.
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PMID:Tachykinin immunoreactivity in the parasitic flatworm Diclidophora merlangi and its fish host the whiting (Merlangius merlangus): radioimmunoassay and chromatographic characterisation using region-specific substance P and neurokinin A antisera. 248 28

Slices of the rat substantia nigra and striatum were superfused in vitro to measure release of tachykinins (TKs). Potassium (30 and 60 mM) infusion caused a 3- to 10-fold outflow of both substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) in the substantia nigra as well as in the striatum as measured by radioimmunoassay. The potassium-evoked release of SP-LI and NKA-LI was significantly, but not completely (by 25-70%) inhibited by simultaneous perfusion with L-glutamic acid (50 microM) and gamma-aminobutyric acid (GABA, 50 microM) in the substantia nigra. No significant inhibition was, however, observed in the striatum. The present data indicate a differential regulation of tachykinins in the striatum and substantia nigra by L-glutamic acid and GABA. The presynaptic regulation of TK release may therefore differ in the dendritic and terminal region of the striatonigral pathway.
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PMID:Effects of GABA and L-glutamic acid on the potassium-evoked in vitro release of substance P- and neurokinin A-like immunoreactivities are different in the rat striatum and substantia nigra. 248 28

Microdialysis combined with radioimmunoassay was used to measure the release of neurokinin A-like immunoreactivity (NKA-LI) in the rat brain in vivo. The effect of a single dose of amphetamine (2 mg/kg s.c.) on the basal overflow and the potassium-induced release of NKA-LI was assessed in the nucleus accumbens and caudate-putamen. Amphetamine potentiated the potassium-stimulated release of NKA-LI by 71% in the nucleus accumbens, while no significant change was observed in the caudate-putamen. Amphetamine did not affect the basal NKA-LI overflow.
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PMID:Amphetamine facilitates the in vivo release of neurokinin A in the nucleus accumbens of the rat. 254 Sep 96

The most widely used smooth muscle preparations for neurokinin bioassays have been critically analyzed in order to determine whether neurokinins act directly or by the intermediary of other natural agents. Indeed, part of the contraction of the GPI in response to neurokinins appears to be mediated by acetylcholine and possibly prostaglandins. Active metabolites of the arachidonic acid cascade also intervene in the response of the HUB. Neurokinins produce relaxation of the DCA by stimulating the release of a vascular smooth muscle relaxing factor from the endothelium. In the other preparations (the RD, the RPA without endothelium and the RPV) neurokinins may act directly on the smooth muscle fibers. Neurokinins produce their biological effects by activating specific receptors. Three different receptor types, one for each mammalian neurokinin, have been identified by using four groups of natural peptide sequences and some selective agonists. The receptor for SP is particularly sensitive to SP and physalaemin and shows higher affinity for the whole natural peptides (SP, NKA) than for their C-terminal fragments. The receptor for neurokinin A is highly sensitive to NKA and eledoisin: it shows high affinity for heptapeptide fragments such as NKA4-10 and SP5-11. The receptor for NKB is sensitive to NKB and kassinin more than to the other natural peptides and their fragments. The natural peptides show however little selectivity. Synthetic analogues active on a single receptor type (selective agonists) have been used to find out whether the responses of the isolated organs are due to the activation of one or more than one receptor. It has been found that the GPI, the RD and the HUB contain all three or at least two receptors, while the DCA has only the NK1, the RPA has only the NK2 and the RPV only the NK3 type. Binding sites specific for each neurokinin have been identified in brain and peripheral organs with accurate biochemical assays, using labeled neurokinins. Competitive displacement assays have been performed with a variety of neurokinin-related peptides, and their Ki have been determined. By plotting Ki values against the ED50, estimated from biological assays, positive significant correlations have been found for the monoreceptor (DCA, RPA, RPV) but not for the multiple receptor systems (GPI, RD, HUB). This suggests that pharmacological receptors may be identical with the recognition sites which bind the labeled neurokinins. The availability of monoreceptor systems and of selective agonists opens the way for the identification of potential antagonists and accurate estimation of their affinities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Receptors for substance P and related neurokinins. 254 98

A structure-activity study on neurokinin A and its C-terminal fragment NKA (4-10) has been performed in order to find selective agonists for the NK-2 receptor and identify chemical modifications suitable for protecting the peptides from degradation, while maintaining activity. Five series of compounds have been prepared and tested: 1. the complete series of the L-Ala monosubstituted analogues of NKA; 2. a series of NKA fragments from the C- or N-terminal; 3. the complete series of NKA (4-10) analogues monosubstituted with beta-Ala; 4. a series of NKA (4-10) analogues with monosubstitutions in pos. 4, 8, 10 or multisubstitutions in two or more of the same positions; and 5. a series of 6 NKA (4-10) analogues monosubstituted with 1-amino,1-cyclohexane carboxylic acid residue. It has been found that the most selective agonists for the NK-2 receptor system are [beta Ala8]NKA (4-10) and [Nle10]NKA (4-10). Protection from aminopeptidase may be obtained by acetylation of the N-terminal amide of NKA (4-10), while partial protection from endopeptidases should be expected from the presence of beta-Ala in position 8. Conformational constraints induced with 1,amino,1-cyclohexane carboxylic acid residue gave weakly active compounds. Multiple substitutions reduce rather than potentiating the favorable effects of the corresponding monosubstituted compounds.
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PMID:Structure-activity studies of neurokinin A. 254 91

Replacement of the glycine in position 8 of the C-terminal heptapeptide NKA(4-10) with beta-alanine give rise to a potent and selective agonist for the NK-2 tachykinin receptor. The affinity of [beta-Ala8]-NKA(4-10) to the NK-2 receptor is enhanced by almost one order of magnitude as compared to NKA(4-10), while affinity decreases at about the same extent at NK-1 and NK-3 receptors, respectively. Synthesis and biological activities of a series of NKA(4-10) analogues systematically replaced in each position with beta-alanine are also reported.
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PMID:A potent and selective agonist for NK-2 tachykinin receptor. 255 Sep 11

The presence and distribution of peptide-containing nerve fibres and axon terminals have been studied in the proximal part of the superior mesenteric artery (SMA) (i.e. conductance vessel) and in the finer ramifications of the SMA close to the intestine (outer diameter 200 microns, i.e. resistance vessel). Light microscopic immunocytochemistry revealed that the proximal part of the SMA possessed a rich supply of neuropeptide Y (NPY)- and tyrosine hydroxylase (TH)-immunoreactive nerve fibres, forming a loose perivascular network which increased in density distally. The vasoactive intestinal peptide (VIP) immunoreactivity was moderate in the proximal artery and only a few VIP fibres could be identified in the distal portion of the SMA. Calcitonin gene-related peptide (CGRP)-, neurokinin (NK)- and substance P (SP)-immunoreactive fibres had an intermediate density in both arterial regions, but their distribution pattern varied. Electron microscopic immunocytochemistry showed that NPY-immunoreactive nerve terminals were close to the smooth muscle cells of the medial layer in both parts of the SMA, indicative of a vasomotor role. Although the VIP-immunoreactive terminals had a similar localization they were seen less frequently. CGRP-, NK- and SP-immunoreactive axons had an identical distribution in the two vascular regions. Interestingly, they were usually seen more distant from the medial layer, localized in the adventitia. Examination of vasomotor responses to perivascular peptides revealed significant regional differences: NPY produced only weak contractions (13 +/- 3%) of proximal vessel segment of the conductance type, while strong concentration-dependent contractions were seen in distal parts of the SMA (resistance vessel). In neither region was any interaction with noradrenaline demonstrated. Proximal segments of the SMA revealed a stronger and more potent response to VIP and peptide histidine isoleucine than did distal segments, while on the other hand acetylcholine was more potent and elicited stronger effects in distal segments. CGRP, NKA and SP relaxed precontracted arteries by 50-75% and there was no significant difference in responsiveness to these peptides in the two regions of the SMA.
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PMID:Comparison of peptidergic mechanisms in different parts of the guinea pig superior mesenteric artery: immunocytochemistry at the light and ultrastructural levels and responses in vitro of large and small arteries. 262 2

Female BALB/C mice were immunized with various neuropeptides and later tested on a hot plate apparatus for responses to nociceptive stimuli. Animals immunized with substance P, neurokinin B (NKB) or fragments of either peptide were found to spend significantly longer periods of time on the hot plate than controls. Subjects treated with substance K (NKA), its N-terminal fragment or neuropeptide Y were not different from controls. Finally, mice injected with histamine or the EXON-4-related peptide were also found to exhibit delayed responses in this test situation. These results suggest roles for SP, NKB, EXON-4-related peptide and histamine in sensory processing and transmission.
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PMID:Diminished nociceptive response in mice following immunization with neurokinins. 274 24

Subcutaneous pretreatment of rats with neurokinin (NK) A or the fragment NKA(4-10) reduced the degree of gastric lesions induced by oral administration of 96% ethanol. The protective effect of NKA(4-10) was dose-dependent. Arg-NKB, the water soluble derivative of NKB, was less effective than NKA or NKA(4-10) while [Me-Phe7]NKB, substance P (SP) and SP-methyl-ester were inactive. The NKA(4-10) antilesion effect was reversed by pretreatment with N-ethyl-maleimide, suggesting a possible involvement of sulphydryls in its action. Among the nonmammalian tachykinins, kassinin significantly reduced ethanol-induced lesions while eledoisin and physalaemin at equivalent molar doses were inactive. These results provide, for the first time, evidence that tachykinins and their derivatives exert gastroprotective activity toward ethanol-induced haemorrhagic lesions. Assuming a receptor-mediated mechanism, NK-2 sites could be involved.
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PMID:Tachykinins protect against ethanol-induced gastric lesions in rats. 274 26


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