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)

1. The possible existence of multiple receptors for substance P (SP) was investigated by examining the relative pharmacological potencies of SP and related peptides in contracting guinea pig ileum, in potentiating electrically evoked contractions of rat vas deferens preparations and in competing for 3H-SP receptor binding in rat brain membranes, and by comparing the extent of cross-tachyphylaxis of various analogues with SP in the guinea pig ileum. 2. Different rank orders of potencies were observed among SP, its C-terminal fragments, analogues and related tachykinins in the different test systems, and these could not be explained by differential access to the target organ receptors. 3. In contrast to SP and physalaemin, both eledoisin and a metabolically stable SP analogue, [pGlu5, MePhe8, Sar9]-SP5-11 exhibited differential recovery from SP tachyphylaxis in the guinea pig ileum, and part of their spasmogenic action in this preparation was atropine-sensitive. 4. The results suggest the possible existence of multiple SP receptors, and the specificity of those in the brain may be different from those in the gut. The structural and pharmacological basis for subdividing tachykinins into SP-physalaemin and eledoisin-kassinin families is also discussed.
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PMID:The possible existence of multiple receptors for substance P. 617 85

Naloxone causes a tonic contraction (= "gut dependence") of the ileum in morphine-dependent rats. This "gut dependence" can be antagonized by morphine (2.5 X 10(-7) g/ml). Substance P-undecapeptide (SP1-11) produces a tonic contraction of the ileum in morphine-independent rats and also in morphine-dependent rats. In the latter, this tonic contraction is comparable with the naloxone-induced contraction. When morphine-dependent rats with naloxone-induced "gut dependence" are given SP1-11, they show an additional increase in tonus followed by a rapid tonus inhibition. Substance P-heptapeptide (SP5-11) also causes a naloxone-like contraction in both the morphine-dependent and the morphine-independent rats. In contrast to SP1-11, SP5-11 produces neither a tonus superposition nor a tonus inhibition in morphine-dependent rats with naloxone-induced "gut dependence". The fact that SP5-11 does not, in contrast to SP1-11, exert these two effects (tonus superposition and subsequent tonus inhibition) is indicative of differences between the mechanisms of the two Substance P sequences.
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PMID:[Differences in activity between substance P and substance P-heptapeptide as studied on the phenomenon of "gut dependence" in rats (author's transl)]. 618 Apr 43

The thermoregulatory effects of intraperitoneally administered substance P (SP1-11) (250 micrograms/kg), or equimolar quantities of SP1-4 and SP5-11 were studied in conscious rats at an ambient temperature of 4 degrees C. SP1-11 produced hypothermia, whereas SP1-4 and SP5-11 had no influence. The hypothermic effect of SP1-11 was partially antagonized by naloxone. Thus, an opiate-dependent step seems to be involved in the action of SP1-11.
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PMID:Effects of substance P and shorter analogs on body temperature in the rat. 618 55

Explants of the ganglion trigeminale (PNS) and of the telencephalon (CNS) from chick embryos were cultivated in MAXIMOW chambers in semisynthetic media in the presence of dipeptide fragments (Lys(Z)-Pro . HCl, Lys-Pro-2HBr, Arg-Pro-2HCl) and the heptapeptide (SP5-11) of substance P as well as the complete substance P (SP1-11). 1. Histological examination of the dipeptide-treated CNS explants indicates that the structure of outgrowth in vitro is changed. Fascicel were observed. A stimulation of nerve fibre extension did not take place. 2.1. In dipeptide-treated PNS cultures the index of areas covered by the explants increased. 2.2. The index of nerve fibre growth increased significantly. The stimulation was caused in multiplication of fibres. Only Lys(Z)-Pro . HCl presents a prolongation of neurites. 2.3. SP5-11 effects in no case the growth of nerve fibres. SP1-11 stimulated significantly the fibre regeneration. 3. The possible role of SP1-11 with different effects under in vitro conditions is discussed. Only the N-terminal dipeptides stimulate the growth of nerve fibres. The C-terminal SP5-11 is without effect. Finally it is stated that the best results in neuritic enlargement and neurogenesis can only be obtained by cultivation with SP1-11.
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PMID:[The effect of substance P (SP) and SP partial sequences on nerve fiber growth in tissue culture]. 618 4

The release of substance P (SP) and two analogues by iontophoresis or pressure from microelectrodes was compared. Substance P was released linearly by iontophoresis from electrodes while no release of the analogues was detected. [N-methylphenylalanine8, N-methylglycine9-] SP5-11 (DiMeC7) and [methyl-2-aminoethyl]11 SP (SP-DAE) were released from electrodes by pressure ejection with linear relationships in all cases between pressure and the amounts released. Under the tested experimental conditions, release of substance P by iontophoresis was between 2 and 3 orders of magnitude less than that by pressure over a given time. The release of substance P and the uncharged analogue DiMeC7 by pressure was very similar while release of SP-DAE was one order of magnitude less.
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PMID:A comparison of the release of substance P and some synthetic analogues from micropipettes by microiontophoresis or pressure. 619 70

Intracerebroventricularly administered Arg-Pro-Lys-Pro-Gln-Gln-Phe-Gly-Leu-Met-NH2 (substance P, SP) enhanced the accumulation of DOPA after inhibition of the aromatic L-amino acid decarboxylase in the rat brain. SP also stimulated locomotor activity in a dose-dependent manner. A total of 31 structural analogues of SP were evaluated with respect to the action on brain monoamine synthesis as well as on locomotor activity. Catecholamine synthesis: SP1-10 was inactive which indicated that the [Met11]-NH2 terminal is essential for biological activity; [Leu10], [Phe7] and [Gln6] were also essential for activity; the minimum length requirement for activity was a hexapeptide amide structure. D-Amino acids in positions 8 or 9 increased activity. [D-Pro2]p-SP and [pGlu5, Gly7]-SP5-11 were active in the dopamine-rich areas, but inactive in the noradrenaline (norepinephrine)-predominant parts of the brain. The inactive [Ile7]-SP potentiated the effect of SP. Neither SP nor its analogues, with the exception of [Lys5,D-Leu8,D-Phe9]-SP5-11, increased the synthesis of 5-hydroxytryptophan (5-HTP). Locomotor activity: SP1-10 and [D-Phe9]-SP were as active as SP; [Ile7]-SP and [Ile7, Ile8]-SP were inactive and they did not antagonize the effect of SP. The results indicate that after chemical manipulation of the SP molecule it is possible to obtain great variation in activity and to dissociate to some extent the behavioural effects from those on brain catecholamine synthesis.
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PMID:Substance P: structural requirements for the activation of brain catecholamine synthesis and locomotor activity in rats. 619 36

The effect of peptides (SP1-2, SP3-4 and SP5-11) of substance P (SP1-11) on the morphology of the areas of growth of explants of the ganglion trigeminale from chick embryos after incubation in Maximow chambers was observed. N- and C-terminal sequences effected the growth of cultures differently. In dipeptide-treated (= N-terminal sequences) cultures the areas of growth increased. In heptapeptide-treated cultures (= C-terminal sequence SP5-11) the areas of growth decreased. Only the dipeptide SP3-4 effects a mitogenic effect on nonneuronal cells in short time tests. The C-terminal sequence SP5-11 stimulates neither the growth of nerve fibres nor the proliferation of cells. Finally the importance of this in-vitro-tests in relation to the in-vivo-situation is discussed.
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PMID:[The effect of N and C terminal sequences of substance P on non-neuronal cells in vitro (nerve tissue culture)]. 620 72

Angiotensin I converting enzyme (ACE) and neutral endopeptidase ("enkephalinase"; NEP), were purified to homogeneity from human kidney. NEP cleaved substance P (SP) at Gln6-Phe7,-Phe8, and Gly9-Leu10 and neurotensin (NT) at Pro10-Tyr11 and Tyr11-Ile12. NEP hydrolyzed 0.1 mM SP, NT and their C-terminal fragments at the following rates (mumol/min/mg): SP1-11 = 7.8, SP4-11 = 11.7, SP5-11 = 15.4, SP6-11 = 15.6, SP8-11 = 6.7, NT1-13 = 2.9, and NT8-13 = 4.0. Purified ACE rapidly inactivated SP as measured in bioassay. HPLC analysis showed that ACE cleaved SP at Phe8-Gly9 and Gly9-Leu10 to release C-terminal tri- and dipeptide (ratio = 4:1). The hydrolysis was Cl- dependent and inhibited by captopril. ACE released mainly C-terminal tripeptide from SP methyl ester, but only dipeptide from SP free acid. Modification of arginine residues in ACE with cyclohexanedione or butanedione similarly inhibited hydrolysis of SP, bradykinin and Bz-Gly-Phe-Arg (80-93%) indicating an active site arginine is required for hydrolysis of SP. ACE hydrolyzed NT at Tyr11-Ile12 to release Ile12-Leu13. SP, NT and their derivatives (0.1 mM) were cleaved by ACE at the following rates (mumol/min/mg): SP1-11 = 1.2, SP methyl ester = 0.7, SP free acid = 8.5, SP4-11 = 2.4, SP5-11 = 0.9, SP6-11 = 1.4, SP8-11 = 0, NT1-13 = 0.2, and NT8-13 = 1.3. Peptide substrates were used as inhibitors of ACE (substrate = FA-Phe-Gly-Gly) and NEP (substrate = Leu5-enkephalin).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydrolysis of substance p and neurotensin by converting enzyme and neutral endopeptidase. 620 35

Behavioral sensitization to kainic acid (KA) in the mouse spinal cord appears to be mediated by the amino (N) terminus of substance P (SP), as potentiation of KA is sensitive to capsaicin, mimicked by SP1-7 but not SP5-11, and blocked by SP1-7 antagonists but not by neurokinin antagonists. As naloxone inhibits some effects of SP1-7, this study examines the role of opioid receptors in the mediation of KA-induced sensitization by the N terminus of SP. All drugs were injected i.t. Behavioral sensitization to repeated injections of KA was inhibited by a large (1 micrograms) dose of naloxone. Pretreatment with either naloxonazine or beta-funaltrexamine, mu-selective opioid antagonists, naltrindole, a delta-selective opioid antagonist, or nor-binaltorphimine, a kappa-selective antagonist, failed to alter the development of sensitization to KA, indicating that this phenomenon is not due to mu, delta, or kappa opioid receptors. The ability of 22.5 pmol of SP1-7 to enhance subsequent KA responses was blocked when coadministered with 0.1 micrograms of naloxone. When administered with KA, naloxone not only failed to reverse the potentiative effect of SP1-7, but further enhanced responses to KA for 2 hr after SP1-7. In contrast to pretreatment with SP1-7, coadministration of KA with SP1-7 inhibited the intensity of behaviors. The inhibitory effect of SP1-7 on responses to a single injection of KA was prevented by pretreatment with naltrindole, whereas pretreatment with beta-funaltrexamine blocked the inhibitory effect of SP1-7 on response to KA in a KA-sensitized animal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of kainic acid-induced activity in the mouse spinal cord by the amino terminus of substance P: sensitivity to opioid antagonists. 768 11

Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.
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PMID:Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats. 917 5


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