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)

Striatal slices from the rat were continuously superfused with [3H]tyrosine in order to estimate the release of newly synthesized [3H]dopamine [( 3H]DA). Substance P (SP) and neuromedin K (NKB) stimulated the spontaneous release of [3H]DA when used in concentrations (from 10(-9) M to 10(-7) M). The stimulatory effect of substance P (10(-8) M) was prevented completely when slices were superfused with tetrodotoxin (10(-7) M) or the substance P antagonist (D-Arg1,D-Pro2,D-Trp7,9,Leu11) substance P (10(-5 M) indicating that the response evoked by substance P was mediated by substance P receptors but that these were not located on DA nerve terminals. In addition, substance P did not modify the stimulatory effect of acetylcholine (ACh) (10(-5) M) on the spontaneous release of [3H]DA since the effects of substance P (10(-7) M) and ACh (10(-5) M) were additive.
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PMID:Stimulatory effect of substance P on the spontaneous release of newly synthesized [3H]dopamine from rat striatal slices: a tetrodotoxin-sensitive process. 243 Feb 28

Antidromic stimulation of sensory nerves or administration of capsaicin and SP in the guinea-pig induced vascular protein leakage with a similar pattern of distribution in different peripheral organs, characterized by a wide-spread but highly selective occurrence. The protein-extravasation responses in the tissues, following nerve stimulation or i.v. capsaicin, were highly correlated with the concentration of SP-LI. Systemic capsaicin treatment caused an almost total loss of SP-LI in visceral organs, in which the extravasation responses to capsaicin or nerve stimulation were also abolished. The ureter of the guinea-pig was most densely innervated by capsaicin-sensitive sensory nerves, which arrive at the rostral part of the ureter via the inferior mesenteric ganglion. The caudal ureter was mainly innervated from the pelvic nerves. The vascular permeability increase induced by SP or capsaicin was more pronounced in the ureter than in any other organ investigated. SP-LI, TK-LI and CGRP-LI coexist in sensory neurons of the guinea-pig and man, as shown by immunohistochemistry. These three kinds of immunoreactivity were found in sensory cell bodies with similar regional and terminal distribution patterns in both the central and peripheral areas. Systemic capsaicin treatment induced marked reduction of SP- and TK-LI in peripheral organs except for the ileum. CGRP-LI in the ureter was also sensitive to the capsaicin treatment. Characterization of the TK-LI (K12) of the guinea-pig ureter and lung, using ion-exchange chromatography and HPLC, demonstrated that at least three immunoreactive components corresponding to NKA, NPK and ELE were present. The major form of SP-LI eluted in the same position as synthetic SP. The NKA- and ELE-like components were also identified by HPLC in water extracts of human ureter. NKB was not detectable in the sensory neurons of the guinea-pig. Capsaicin caused an acute release of SP-, NKA- and ELE-like components from superfused slices of both the spinal cord and ureter of the guinea-pig in vitro. The release of tachykinins by capsaicin was calcium-dependent but tetrodotoxin-resistant. No detectable release of NKB- or NPK-LI was induced by capsaicin. Tachykinins share a common spectrum of biological activities with regard to hypotension, bronchoconstriction and protein extravasation when given systemically to guinea-pigs. The potency of the hypotensive action of tachykinins was similar. NKA and NPK evoked much stronger bronchoconstrictor effects than SP, while SP was more active than NKA in inducing vascular permeability changes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tachykinins and calcitonin gene-related peptide in relation to peripheral functions of capsaicin-sensitive sensory neurons. 243 Apr 27

Neurokinin A and B (NKA and NKB) and neuropeptide K (NPK) were recently isolated from porcine spinal cord and brain, and together with substance P (SP) considerably extend the list of tachykinin-like peptides present in the mammalian nervous system. In order to investigate the distribution of tachykinins in the central nervous system (CNS) we have recently developed sensitive radioimmunoassays (RIA) for both SP and NKA. As NKB and NPK cross-react in the RIA for NKA we were able to determine the content of NKA, NKB and NPK after separation of rat CNS extracts by reverse-phase high-performance liquid chromatography (HPLC). Comparison of different extraction methods suggested that 0.1 M hydrochloric acid gave the best extraction and recovery of NKA-like immunoreactivity from rat brain. Characterization of these tachykinins using HPLC and gel-filtration columns revealed that C18 columns did not adequately separate NPK from NKB under the conditions used by previous authors. Thus 'NKB' content reported previously on the basis of HPLC separation would correspond to the sum of both NPK and NKB content. In the present study, therefore, we introduced modified elution conditions to resolve NPK from NKB and determined the regional distributions of these tachykinins in the rat CNS. SP was the most abundant tachykinin in every region studied. After SP, the NKA concentration was highest and NKB concentration was lowest in all regions except for the cortex and hippocampus where the NPK concentration was highest. The molar ratio of these peptides seemed to be relatively constant in the 3 regional groups (striatum-substantia nigra, cerebral cortex-hippocampus, dorsal root ganglia-dorsal and ventral horns of spinal cord) and suggests that regional specific translation or processing may exist.
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PMID:Regional distribution of neuropeptide K and other tachykinins (neurokinin A, neurokinin B and substance P) in rat central nervous system. 243 60

The effects of several protein modifying reagents, including phenoxybenzamine, N-ethylmaleimide (NEM), 5,5'-dithiobis (2-nitro)--benzoic acid (DTNB), p-chloromercuryphenyl sulfonic acid (PCMP) and p-bromophenacylbromide (PBPB), on the binding of 125I-Bolton Hunter substance P (125I-BHSP), 125I-Bolton Hunter eledoisin (125I-BHELE) and 3H-neurokinin B (3H-NKB)4 to cortical synaptosomes were examined. PCMP (10(-4) M), DTNB (10(-4) M) and NEM (10(-3) M) were without effect on the 125I-BHSP binding but reduced markedly the specific binding of 125I-BHELE or 3H-NKB. Although phenoxybenzamine and PBPB inhibited the 125I-BHSP binding when used in high concentrations (10(-4) M and 10(-3) M), they were more potent in inhibiting the 125I-BHELE or 3H-NKB binding. These results indicate that the NKB binding site is more sensitive to alkylating reagents than the SP binding sites and that these reagents can be used to distinguish SP and NKB receptors in the brain.
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PMID:Sulfhydryl reagents have different effects on substance P and neurokinin B binding sites on cortical synaptosomes in the rat. 243 90

Contractile responses to neurokinin alpha and neurokinin beta were characterized and compared with those to substance P (a SP-P agonist) and eledoisin (a SP-E agonist) in isolated rabbit iris sphincter. Neurokinin alpha and neurokinin beta as well as substance P and eledoisin produced atropine- and tetrodotoxin-resistant contractions of the iris sphincter in nanomolar concentrations, and the rank order of sensitivity was eledoisin greater than substance P = neurokinin alpha = neurokinin beta. After prolonged cold-storage of the preparations, responses to capsaicin, a releaser of tachykinins from sensory nerve endings, were nearly absent, but responses of considerable magnitude to carbachol and the tachykinins persisted. On wash-out of the tachykinins, responses faded at characteristic rates (neurokinin alpha greater than eledoisin greater than neurokinin beta much greater than substance P). From the Schild analyses, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P, a potent substance P antagonist, competitively antagonized the response to substance P, had no significant effect on the response to neurokinin beta, and antagonized the response to neurokinin alpha and eledoisin in a more complex manner. Taken together, these results suggest that there coexist multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.
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PMID:Pharmacological evidence for the possible coexistence of multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle. 243 60

The effects of subchronic (14 day) treatment with the inhibitors at the uptake of monoamines, zimelidine, alaproclate and imipramine, on regional levels of substance P (SP) and other tachykinins in tissue in the central nervous system of the rat were studied by radioimmunoassay. In the ventral spinal cord, in which substance P is known to exist together with 5-hydroxytryptamine (5-HT), in the terminals of descending neurones, treatment with the selective inhibitors of the uptake of 5-HT zimelidine (2 X 10 mumol/kg p.o.) or alaproclate (2 X 10 mumol/kg or 2 X 20 mumol/kg p.o.), increased the level of substance P-like immunoreactivity (SP-LI). The effect of alaproclate appeared to be dose-dependent. After treatment with imipramine (2 X 10 mumol/kg p.o.) only a tendency to increased levels of substance P-like immunoreactivity spinal cord was seen. Treatment with alaproclate, at the highest dose level, also elevated the concentration of neurokinin A/neurokinin B-like immunoreactivity (NKA/NKB-LI) in the ventral spinal cord. In the frontal cortex, in which separate monoaminergic and tachykinin-containing neurones interact, treatment with imipramine reduced the levels of SP-LI and NKA/NKB-LI, while treatment with alaproclate had the opposite effect. In the periaqueductal grey matter, treatment with zimelidine and alaproclate increased the levels of SP-LI and NKA/NKB-LI, while treatment with imipramine increased only the level of NKA/NKB-LI. In conclusion, subchronic treatment of rats with inhibitors of the uptake of monoamines induced changes in levels of tachykinin in frontal cortex, periaqueductal grey and spinal cord. The selective inhibitors of the uptake zimelidine and alaproclate, had similar effects on levels of tachykinin, while the inhibitor of the uptake of 5-HT and noradrenaline, imipramine induced changes in the frontal cortex, which were qualitatively different from the effects of zimelidine and alaproclate. Furthermore, the levels of different tachykinins were not always changed in parallel by the same treatment.
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PMID:Effects of subchronic treatment with imipramine, zimelidine and alaproclate on regional tissue levels of substance P- and neurokinin A/neurokinin B-like immunoreactivity in the brain and spinal cord of the rat. 243 37

Plasma protein extravasation was studied in the rat abdominal skin. Substance P (SP), neurokinin A (NKA) and B (NKB) were found to induce extravasation with a threshold dose of about 1 pmol. Calcitonin gene-related peptide (CGRP) caused no or little extravasation alone but it potentiated the action of SP, NKA, NKB, and physalaemin. The potentiation of the SP-induced extravasation was unaffected by pretreatment with capsaicin, indomethacin or compound 48/80, it was reduced by neuropeptide Y or pretreatment with mepyramine plus cimetidine, and was abolished in streptozotocin diabetic rats. CGRP augmented extravasation induced by histamine, reduced the effect of ATP or adenosine and did not alter extravasation by serotonin, bradykinin or neurotensin. These results indicate that in addition to SP the novel mammalian tachykinins NKA and NKB may be considered as mediator candidates for neurogenic plasma extravasation. CGRP is a possible mediator of antidromic vasodilation. Furthermore, CGRP potentiates the extravasation caused by coexisting tachykinins and could thereby augment neurogenic inflammation. The diverse interactions of CGRP with other inflammatory mediators suggest multiple sites of action.
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PMID:Several mediators appear to interact in neurogenic inflammation. 244 66

Two categories of peptides exert opposing effects on the isolated guinea pig trachea. Neurokinins (substance P [SP] and congeners) provoke contraction, and kinins (bradykinin) provoke relaxation. Both peptide categories promote the release of relaxing prostaglandins that oppose the contractions induced by neurokinins and mediate entirely the relaxations by the kinins. Receptors for neurokinins have been characterized by comparing the effects of a variety of agonists (naturally occurring or synthetic peptides) in the guinea pig trachea and in other selective preparations. It has been found that the guinea pig trachea contains receptors for neurokinin A (NKA) and for substance P. This has been demonstrated by showing that selective activators of the neurokinin A receptor type are potent stimulants of contraction, and that selective stimulants of the receptors for SP are also active contractile agonists. The order of potency for the neurokinins is NKA greater than NKB greater than SP. The relaxations of guinea pig trachea provoked by bradykinin is not due to the activation of B1 or B2 receptors since it is not modified by specific B1 or B2 antagonists. It is suggested that bradykinin may promote the release of prostaglandins either through a third receptor or by an unknown mechanism. These studies show that the isolated guinea pig trachea is a complex preparation, composed of various tissues and containing different types of neurokinin receptors. The preparation also contains endogenous active agents (e.g., prostaglandins) that are released by the peptides and that may modify or partially or entirely mediate the biologic effects of peptides.
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PMID:Peptide receptors in the airways. 244 39

The autoradiographic localization of [125I]Bolton-Hunter substance P (BHSP) was examined in slide-mounted sections of dog kidney and dog renal artery and vein. Biochemical characterization of the binding in sections of dog kidney, demonstrated that BHSP binds to a population of non-interacting sites with high affinity (KD = 0.11 +/- 0.02 nM, Bmax = 0.29 +/- 0.05 fmol/section). The binding was displaced by tachykinins in the order SP greater than NKA much greater than NKB, indicative of binding to NK-1 receptors. BHSP binding to dog kidney was localized over glomeruli and endothelium of intrarenal arteries. There was binding associated with the endothelium and adventitia of the renal artery but not the vein. Binding of BHSP to arcuate arteries and to the renal artery was dependent on the presence of an intact endothelium. No evidence was obtained for receptors associated with any renal tubules. These results suggest that in the dog, vasodilation, diuresis and natriuresis in response to SP may result from an action primarily on the vascular elements of the kidney.
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PMID:Autoradiographic localization and characterization of substance P binding in dog kidney. 244 48

The contractile response to substance P (SP), neurokinin A (NKA) and arginin-neurokinin B (Arg-NKB) (a water soluble analogue of NKB) was investigated in detrusor muscle strips from the dome of the urinary bladder obtained from patients undergoing total cystectomy for carcinoma of the bladder base. Spontaneous activity and response to nerve stimulation indicated that the material used in this study has characteristics similar to those described for 'normal' human detrusor muscle. All neurokinins induced a concentration-related contraction with sensitivity at nM concentrations and the following rank order of potency: NKA (90) greater than Arg-NKB (22) greater than SP (1). These findings indicate the involvement of NK-2 receptors in the contractile response of human detrusor muscle to neurokinins.
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PMID:Contractile response of the human isolated urinary bladder to neurokinins: involvement of NK-2 receptors. 245 Jul 65


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