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)

The effects of substance P, neurokinin A, neurokinin B, [Sar9, Met(O2)11]-substance P, [Nle10]-neurokinin A (4-10) and senktide (succinyl-[Asp6, MePhe8]-substance P (6-11)) on blood pressure and heart rate were studied in anesthetized dogs. Dose-dependent decreases in blood pressure and increases in heart rate were caused by each peptide except senktide. The latter elicited weak hypotensive or hypertensive responses at high doses. The order or potency was as follows: [Sar9, Met(O2)11]-substance P greater than or equal to substance P greater than neurokinin A greater than neurokinin B greater than [Nle10]-neurokinin A (4-10) much greater than senktide. CP-96,345, [(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine] a selective NK-1 tachykinin receptor blocker, inhibited substance P-induced hypotension in a dose-related manner. Responses to each of the other peptides were inhibited by CP-96,345, 1.0 mg/kg (excluding senktide against which CP-96,345 was not tested). CP-96,344 (1.0 mg/kg i.v.) the 2R-3R enantiomer of CP-96,345 which does not block NK-1 receptors, had no effect on substance P-induced hypotension. We conclude that tachykinin-induced hypotension in dogs is mediated by NK-1 tachykinin receptors.
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PMID:Inhibition of tachykinin-induced hypotension in dogs by CP-96,345, a selective blocker of NK-1 receptors. 172 63

The vasoactive properties of the neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB)) and some selective analogues were assessed in the arterial and venous mesenteric beds of the rat. Although both sides of the mesenteric vasculature displayed endothelium-dependent relaxation in response to acetylcholine (ACh) or bradykinin (BK) (1 and 10 nmol), SP and the selective NK-1 analogue, [Sar9,Met(O2)11]SP were inactive. Of the three selective neurokinin agonists used, [Sar9,Met(O2)11]SP (NK-1), [beta-Ala8]NKA-(4-10) (NK-2) and [MePhe7]NKB (NK-3), only the latter induced a dose-dependent pressor effect in the venous mesenteric vasculature. Injections of SP and the selective NK-1 and NK-2 analogues at high doses (10 nmol), did not change the perfusion pressure in the mesenteric bed even when the mesenteric vasculature was treated with methylene blue (50 microM) to inhibit the effects of endothelium-derived relaxing factor (EDRF) or with NG-nitro-L-arginine (L-NNA) (20 microM) to inhibit the formation of EDRF or with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate] (CHAPS 20 mM, 30 s) to remove the endothelial layer. In contrast, the vasoconstrictor effects of noradrenaline (NA), angiotensin II (ATII), NKB and [MePhe7]NKB on the venous side of the circulation were enhanced following treatment with L-NNA, methylene blue or CHAPS. The present results suggest that neurokinins act on the rat mesenteric bed by increasing the perfusion pressure of the venous vasculature via activation of NK-3 receptors. Neurokinins are inactive on the arterial mesenteric vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurokinins produce selective venoconstriction via NK-3 receptors in the rat mesenteric vascular bed. 172 50

Cyclic analogues of substance P of the formula cyclo-[Glu-Phe-Phe-Gly-Leu-Met-NH(CH2)nNH-], where n = 3-10, 12, and open-chain analogues (XVIIIa, b) H-Glu.(NHR)-Phe-Phe-Gly-Leu-Met-NHR, where R = -CH3, -CH2CH2CH3, were synthesized. By NMR spectroscopy it was found that cyclo-compounds with n = 3-8 have regularly arranged structures, stabilized by intramolecular hydrogen bonds. Substances of this type showed less than or equal to 0.1% of the substance P activity on the guinea pig ileum, but some of them antagonize the natural peptide (for compound with n = 5 IC50 = 3.2.10(-6) M). The open-chain compounds proved to have rather high myotropic activity, viz., 22% (R = -CH3) and 8% (R = -CH2CH2CH3) of the substance P activity.
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PMID:[Cyclic analogs of substance P. III. Cyclo (6(sup)gamma----oligomethylenediamine----11) substance P(6-11)-hexapeptides]. 172 6

Recent in vitro studies have shown that the dose-response curve of substance P on [3H]protein secretion from rat parotid glands is biphasic. Such a response could result either from the activation of tachykinin receptors or from the amphiphilic character of substance P, since it has previously been shown that the N-terminal part of substance P may play an important role in the activation of phosphoinositides in rat parotid glands. To investigate these possibilities, we studied the effects of selective NK1, NK2, NK3 receptor agonists and C-terminal fragments of substance P and neurokinin A on protein secretion from rat parotid lobules. The poor activity of NK2 (neurokinin A-(4-10) and [beta-Ala8]neurokinin A-(4-10)) as well as of NK3 ([MePhe7]neurokinin B) selective agonists allowed us to rule out a possible involvement of NK2 and NK3 receptors in the parotid gland secretory process. Conversely, the selective NK1 receptor agonist, [Sar9,Met(O2)11]substance P, reproduced the biphasic dose-response curve for [3H]protein secretion typical of native substance P. However, a biphasic response was not observed with peptides deprived of the N-terminal moiety of substance P, such as substance P-(4-11) or [AcArg6,Sar9,Met(O2)11] substance P-(6-11). Our data therefore indicate that the [3H]protein secretion obtained with substance P results from the activation of NK1 receptors. Moreover, our data suggest that the N-terminal tripeptide of substance P is also active, and could stimulate different phospholipases either by acting through a second functional site on the NK1 receptor or by directly activating G-proteins.
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PMID:Involvement of NK1 receptors and importance of the N-terminal sequence of substance P in the stimulation of protein secretion in rat parotid glands. 172 89

Previous work from this laboratory has provided biochemical characterization of several posttranslational processing intermediates of the neuropeptide substance P (SP) in central nervous system (CNS) tissues, including the COOH-terminal glycine-extended dodecapeptide Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-Gly (SP-G). SP-G is a major species of unprocessed SP found in rodent CNS tissues, and is the likely immediate precursor form of SP in the biosynthetic scheme. Here we present extensive characterization of the normal regional distribution of SP-G, as compared to SP, throughout the rat CNS via coordinated biochemical and morphological analyses. By radioimmunoassay (RIA), an approximate 10-fold variation in regional levels of SP-G-like immunoreactivity (SP-G-LI) was observed, ranging from 0.30 pmol/g in the amygdala, to 6.49 pmol/g in the medulla. On a normalized basis, the regional variation of unamidated precursor relative to mature peptide (SP-G-LI/SP-LI molar ratio) ranged from 0.30% in the amygdala to 5.15% in the dorsal root ganglia (DRG). Overall, the highest SP-G-LI/SP-LI ratios were found in DRG, medulla, and spinal cord, i.e. CNS areas associated with primary sensory afferent innervation via capsaicin-sensitive unmyelinated small diameter fibers. In addition, chromatographic and RIA analyses of extracted brain tissues indicated that the quantified immunoreactivities corresponding to SP, SP-G, as well as an additional COOH-terminal Gly-Lys-extended precursor, i.e., SP-G-K, displayed very similar chromatographic behavior as demonstrated for chemically authentic standards. These biochemical data were complemented by immunohistochemical analyses demonstrating a pattern of immunohistochemical staining for the presence of SP-G-LI as a defined subset of SP-LI-containing neural elements. Here, reaction product was localized to dendritic, axonal, and terminal neuronal elements in representative CNS regions of the rat, with relatively high levels of SP-G-LI found within anatomical areas containing a high density of sensory terminal structures. In an attempt to provide correlative functional anatomy, a group of rats was treated with colchicine, in order to differentially localize SP-LI- and SP-G-LI-containing somata after inhibition of axoplasmic transport. Most prominently, colchicine administration engendered immunohistochemical visualization of both SP-LI- and SP-G-LI-positive cells in mesencephalic and brainstem regions associated with stress, pain responses, and central control of autonomic function. Within this context, the coordinate expression of both SP-LI- and of SP-G-LI-positive somata in discrete brain areas is probably indicative of high ongoing rates of tachykinin synthesis coupled to utilization.
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PMID:Biochemical characterization and anatomical distribution of a major form of unamidated precursor of substance P in rat brain. 172 13

Theoretical conformational analysis of C-terminal fragments of tachykinin peptides with a common amino acid sequence Asx-Xaa-Phe-Yaa-Gly-Leu-Met-NH2 suggested the conformational states to be independent of the nature of Xaa and Yaa residues. It is shown that among plausible spatial forms of the C-terminal fragments an alpha-helix with the hydrophobic coat consisted of identically oriented side chains is energetically the most stable structure. The preference of this conformation for tachykinins functioning is discussed.
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PMID:[Conformational analysis of tachykinins. III. C-terminal fragment Asx-Xaa-Phe-Yaa-Gly-Leu-Met-NH2]. 179 35

Membranes isolated from a murine fibroblast B82 cell line (SKLKB82#3) transfected with the bovine stomach cDNA pSKR56S exhibited binding of [His(125I)1]neurokinin A (125I-NKA) to a single population of sites with a Bmax of 147 fmol/mg of protein and a Kd of 0.59 nM. Control cell lines had little or no specific binding. The ligand binding in SKLKB82#3 cells was reversible and was inhibited by peptides in the potency rank of neuropeptide gamma greater than neuropeptide K greater than neurokinin A greater than [10-norleucine]neurokinin A-(4-10) greater than substance P much greater than senktide (succinyl-Asp-Phe-MePhe-Gly-Leu-Met-NH2). Specific binding was enhanced by Mn2+, Mg2+, and Ca2+ and was inhibited by guanine nucleotide analogues. Thus, SKLKB82#3 cells have been transfected with NK2 receptors that have become associated with an endogenous guanine nucleotide-binding protein. In comparison with membranes from the hamster urinary bladder, a tissue enriched in NK2 receptors, NK2 receptor antagonists displayed markedly different potencies, either more or less potent, in inhibiting specific binding in membranes of the transfected cells. Furthermore, inhibition of 125I-NKA binding by nucleotide analogues was markedly different in SKLKB82#3 cells compared with hamster bladder tissue. The different binding profile in the cells is not due to an artefact introduced during cDNA transfection because a similar profile was also observed in bovine stomach membranes. These results may indicate the existence of two distinct NK2 receptors.
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PMID:Characterization of a tachykinin peptide NK2 receptor transfected into murine fibroblast B82 cells. 184 6

Different regions of the prostate gland, namely the prostatic capsule, peripheral prostate, and proximal and distal central prostate, were obtained from 5 patients with carcinoma of the bladder and studied histochemically and immunohistochemically to localise acetylcholinesterase (AChE)-, dopamine beta-hydroxylase (DBH)-, serotonin- and peptide-containing nerves. Autonomic ganglia were found in all regions of the prostate studied. The greatest number of ganglia contained AChE and neuropeptide Y (NPY) followed (in decreasing order) by DBH; [Met]enkephalin (mENK) and [Leu]enkephalin (IENK); calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP); and serotonin, but not somatostatin. The greatest density of nerve fibres was found in the proximal central prostate, followed by the anterior capsule and distal central prostate, with the least in the peripheral prostate. The greatest number of nerve fibres contained ACh and NPY, followed in decreasing order by VIP and DBH; IENK, serotonin and CGRP; mENK; substance P and somatostatin. The functions of the neurotransmitter substances in the human prostate remain to be elucidated.
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PMID:The human prostate gland: a histochemical and immunohistochemical study of neuropeptides, serotonin, dopamine beta-hydroxylase and acetylcholinesterase in autonomic nerves and ganglia. 187 92

Adrenal medullary tissue was collected from parkinsonian patients at autopsy and at the time of autologous transplantation of the adrenal medulla to the caudate nucleus, and from nonparkinsonian patients at autopsy and during nephrectomy. Levels of the following neuropeptides were measured by radioimmunoassay in samples of the medullary tissue: neuropeptide Y (NPY), substance P (SP), [Met]enkephalin ([Met]ENK), vasoactive intestinal peptide (VIP), peptide YY, and bombesin-like immunoreactivity. Regression analysis was used to establish a relationship between patient age, time to organ harvest, and peptide levels in nonparkinsonian tissue. Levels of [Met]ENK, VIP, NPY, and SP were significantly lower in parkinsonian adrenal medullae than that predicted from the control group. These results suggest that the adrenal medulla of a parkinsonian patient is severely compromised, either by the disease process itself or by the antiparkinsonian medications used to treat the symptoms of the disease.
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PMID:Decreased levels of [Met]enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide in parkinsonian adrenal medulla. 191 31

Various peptide derivatives of the C-terminal decapeptide of gastrin releasing peptide (GRP-10) and neuromedin B (NMB), i.e., carboxyl terminal fragments, amino terminal fragments and substituted analogues, were chemically synthesized and the structure-activity relationships of the peptides were investigated by comparing their contractile activities on the rat uterus. Peptides with chain lengths of 8 and 9 amino acid residues from the C-terminus of GRP-10 and NMB, respectively, had considerable contractile activities. At position 6 of both decapeptides, Val seems to be more favourable than Thr for inducing contraction of the rat uterus. The substitution of His at position 3 and Leu at position 9 of GRP-10 by Leu and Phe, as in NMB leads to a decrease in activity. Moreover, Trp at position 4 and -Met-NH2 at the C-terminus are essential for activity. Furthermore, in order to characterize the bombesin-receptor profile of rat uterus, the inhibitory effect of two peptide antagonists, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [Leu13-phi (CH2NH)-Leu14]-bombesin on the contraction of rat uterus were examined.
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PMID:Structure-activity relationships of mammalian bombesin-like neuropeptides in the contraction of rat uterus. 192 98


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