Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis and biological evaluation on thermoregulation of 39 peptides related to bombesin (structural analogues or other naturally occurring peptides) are described. The bioassay system reported measures the ability of peptides injected intracisternally to lower body temperature of cold (4 degrees C) exposed rats. The most potent analogues of bombesin were those in which positions one to five (not included) were altered, indicating that the decapeptide C terminal was sufficient for full potency. Gln at the seventh position and Gly at the 11th position could be replaced by D-Gln and D-Ala (but not D-Pro or D-Phe), respectively, without any change in potency. Methionine at the 14 position could be replaced with its D isomer with retention of 10% biological activity. Any other alteration of the C terminus (deletions or free acid with the exception of the N-methylamide) drastically reduced the biological potency of those peptides. Among other naturally occurring peptides, alytesin was found to have 100% of bombesin potency whereas litorin, neurotensin, xenopsin, substance P, physalaemin, and eledoisin were found to be in the order of 10(4) times less potent. The shortest peptide found to have full biological activity is the octapeptide des-Glp-Gln-Arg-Leu-Gly-Asn[D-Glp7, D-Ala11]-bombesin.
 ...
PMID:Bombesin, bombesin analogues, and related peptides: effects on thermoregulation. 65 96

Secretin, substance P, and vasoactive intestinal peptide (VIP) were studied from the immunological point of view using synthetic hormones and their related peptides which were prepared by the conventional method for peptide synthesis. Immunological properties of these hormones were characterized by radioimmunoassays specific to the respective hormones. Antisecretin antisera (NCC-R-1 and R-801) were generated in rabbits with synthetic porcine secretin absorbed on polyvinylpyrrolidone. Antiserum to substance P (R-400) was produced in a rabbit with synthetic substance P-human alpha-globulin conjugate. Generation of anti-VIP antiserum (R-502) was carried out by immunizing rabbits with synthetic VIP absorbed on polyvinylpyrrolidone. Synthetic polypeptides related to the three hormones that were examined in this study include secretin(4-27), secretin(5-27), secretin(7-27), secretin(11-27), secretin(14-27), secretin(18-27), secretin(1-22)amide, secretin(7-22)amide, Nalpha-tyrosyl-secretin, [1-Tyr]secretin, [4-Ala]secretin, [4-D-Ala]secretin, [4-Ala,5-Val]secretin, [6-Tyr]secretin, substance P(2-11), substance P (3-11), substance P(4-11), substance P(5-11), substance P(6-11), Nalpha-tyrosyl-substance P, [1-Tyr]substance P, [8-Tyr]substance P, [11-Leu]substance P, des-11-Met-substance P, VIP(7-28), VIP(11-28), VIP(18-28), VIP(1-18)amide, and VIP(1-22)AMIDE. The results revealed two antigenic regions at the amino- and carboxylterminal portions of the secretin and VIP molecules. As to substance P, the major antigenic region was located within the 3 to 11 sequence. The proline residue in position 4 and methionine in position 11 seemed to be of special importance. The immunoassays demonstrated the existence of immunoreactivities of these hormones in hot water extracts from various porcine tissues. In the pituitary, VIP and substance P immunoreactivities were detected, whereas secretin was not. Secretin, VIP, and substance P were found in the pancreas, but at low concentrations. Distributions of these hormones in various sites of the gastrointestinal tract were also demonstrated.
 ...
PMID:Immunological aspects of secretin, substance P, and VIP. 83 40

The nature of the interaction between spinally administered opioid and alpha-2 agonists was investigated using the substance P behavioral test in mice. Morphine and agonists which more selectively activate mu or delta opioid receptors were co-administered intrathecally with direct and indirect acting adrenergic agonists norepinephrine, cocaine or clonidine and the behavioral responses to intrathecally coadministered substance P were evaluated. The ED50 values for agonists administered separately and concurrently were computed and drug interactions were evaluated using isobolographic analyses. After separate administration, all the opioid and adrenergic agonists inhibited the substance P-induced behavioral responses. Upon coadministration of opioid and adrenergic agonists, a multiplicative interaction was observed between morphine or the delta agonist D-Pen2-D-Pen-5-enkephalin and the adrenergic agonists. Additive or antagonistic interactions were found between the mu agonist Tyr-D-Ala-NMe-Phe-Gly(ol) and the same adrenergic agonists. The opioid antagonist naloxone and the alpha-2 adrenergic antagonist idazoxan were given as intrathecal pretreatments at doses chosen to shift the dose-response curves of their corresponding agonist (given alone) 4- to 10-fold to the right; this always resulted in a smaller, but significant (2- to 4-fold) shift in the dose-response curve of the other agonist given alone. Intrathecal pretreatment with naloxone or idazoxan altered some interactions between the opioids and clonidine. Although naloxone blocked completely the multiplicative interaction between morphine and clonidine, idazoxan did not. Both naloxone and idazoxan changed the antagonistic interaction between Tyr-D-Ala-NMe-Phe-Gly(ol) and clonidine to a multiplicative interaction. Neither antagonist blocked the multiplicative interaction between D-Pen2-D-Pen5-enkephalin and clonidine. These results suggest that: 1) interactions between opioid and adrenergic agonists in mouse spinal cord are mediated by delta and alpha-2 receptor subtypes; 2) the synergistic interaction between morphine and alpha-2 adrenergic agonists may involve action at delta opioid receptors; and 3) antagonist action on these drug interactions is complex.
 ...
PMID:Spinal interactions between opioid and noradrenergic agonists in mice: multiplicativity involves delta and alpha-2 receptors. 137 95

The D-enantiomer of residues 2, 4, 5, 6, 7, 8, 10 and 11 was introduced in the sequence of Substance P: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2. The achiral glycine residue was replaced by a D-Ala residue. Regarding NK-1 binding potencies or activities, changing to the D-enantiomer in positions 2, 4 or 5 did not modify the pharmacological patterns of the resulting peptides. Introduction of a D-residue in the 6 to 11 sequence drastically decreased the potency of the D-analogues with the exception of [D-Leu10]SP which was found only three times less potent than SP in contracting the guinea-pig ileum. No clear cut evidence between the binding potencies and activities on NK-1, NK-2 and NK-3 assays, was observed which allows a more rational design of tachykinins antagonists.
 ...
PMID:Influence of the replacement of amino acid by its D-enantiomer in the sequence of substance P. 1. Binding and pharmacological data. 171 76

The D-enantiomer of residues 2, 4, 5, 6, 7, 8, 10 and 11 was introduced in the sequence of Substance P: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH1. The achiral glycine was replaced by a D-Ala residue. The conformations of the D-substituted analogues were analysed by NMR and molecular energy calculations. Introduction of a D-amino acid in the address sequence of SP (1 to 5) distorted the helical structure of [D-Pro2]SP and [D-Pro4]SP. A D-glutamine in position 5 hampered the formation of an helix, the core of [D-Gln5]SP was stabilized by the presence of two beta-turns. The exact fitting of both Phe7 and Phe8 in the binding pocket can be achieved by either an alpha- or a 3(10) helix or two beta-turns types I and II'. Replacement of an amino acid in the message sequence, 6 to 11, drastically decreased the potencies of the corresponding analogues, different conformational modifications were observed. [D-Gln6]SP presented two beta-turns, however, the types of beta-turns should orientate the side-chains in such a way that [D-Gln6]SP did not fit in the binding site. The conformations of [D-Phe7]SP and [D-Phe8]SP were completely changed, a more or less extended structure being observed. Modifications in the Gly-Leu-Met-NH2 sequence did not affect the helical structure of the core of [D-Ala9]SP, [D-Leu10]SP and [D-Met11]SP, but decreased the percentage of extended structure of the C-terminal tripeptide.
 ...
PMID:Influence of the replacement of amino acid by its D-enantiomer in the sequence of substance P. 2. Conformational analysis by NMR and energy calculations. 171 77

The neuropeptides substance P, neurotensin and [Met]enkephalin are found in the ventral tegmental area, site of the A10 dopamine cell bodies. Evidence suggests a functional interaction between these peptides and the dopaminergic neurons. All three peptides have been shown to exert an activating effect on these neurons. The present study analyzed the effects of ventral tegmental area infusion of neurotensin, substance P and D-ala-[Met]enkephalin on feeding behavior. These effects were studied in both food-deprived and satiated rats. During a 30 min test, the following parameters were registered: latency to eat, total food intake, food spillage, number of eating bouts and duration of eating. Similar measures were taken for drinking. In deprived rats substance P (0.5, 3.0 micrograms) increased latency to eat but did not affect other parameters, and substance P did not affect eating in satiated rats. Neurotensin (0.5, 2.5 micrograms) increased latency to eat and markedly reduced food consumption in deprived rats and had no effect in satiated rats. D-Ala-[Met]enkephalin (0.1, 1.0 micrograms) stimulated feeding behavior in both deprived and satiated rats. These results show that although the different peptides are presumed to activate the dopaminergic A10 neurons, their effects on feeding behavior can be differentiated. The findings are discussed in terms of motor and motivational mechanisms, and the relative contributions of specific and non-specific influences on feeding are considered.
 ...
PMID:Ventral tegmental area infusion of substance P, neurotensin and enkephalin: differential effects on feeding behavior. 242 71

Superfusion of slices from the dorsal half of the lumbar enlargement of rat spinal cord with Krebs-Henseleit medium supplemented with 30 microM bacitracin allowed the collection of substance P-like immunoreactive material (SPLI), which was released at a rate of approximately 10 pg/4 min. Tissue depolarization by an excess of K+ (30-60 mM) or veratridine (50 microM) induced a marked increase in SPLI outflow, provided that Ca2+ was present in the superfusing fluid. K+- or veratridine-induced SPLI overflow could be modulated in opposite directions by mu and delta opioid receptor agonists. Thus, the two preferential mu agonists Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO; 10 microM) and Tyr-D-Ala-Gly-MePhe-Met(O)5-OH (FK-33824; 0.1 microM) enhanced SPLI overflow from depolarized tissues, whereas the selective delta agonists Tyr-D-Thr-Gly-Phe-Leu-Thr (deltakephalin; 3 microM) and [2-D-penicillamine, 5-D-penicillamine]enkephalin (50 microM) reduced it. The effect of DAGO was antagonized by a low concentration (1 microM) of naloxone but not by the selective delta antagonist ICI-154129 (50 microM). In contrast, the latter drug prevented the inhibitory influence of delta agonists on K+-induced SPLI release. Complementary experiments with morphine (10 microM) and [2-D-alanine, 5-D-leucine]enkephalinamide (3 microM), in combination with 1 microM naloxone or 50 microM ICI-154129 for the selective blockade of mu or delta receptors, respectively, confirmed that the stimulation of mu receptors increased, whereas the stimulation of delta receptors reduced, SPLI overflow. The results suggest that, at the spinal level, and antinociceptive action of delta but not mu agonists might involve a presynaptic inhibition of substance P-containing primary afferent fibers.
 ...
PMID:Opposite effects of delta and mu opioid receptor agonists on the in vitro release of substance P-like material from the rat spinal cord. 243 85

1. Opioid receptors have been demonstrated on sensory fibres in the vagus nerve. Non-cholinergic (NC) neural bronchoconstriction in guinea-pig is due to release of neuropeptides from sensory nerve endings. We have therefore studied the effect of opioids on this NC bronchoconstriction in the anaesthetized guinea-pig. 2. Bilateral vagal stimulation (5 V, 5 ms, 10 Hz) caused reproducible bronchoconstriction in guinea-pigs which was reduced by atropine (1 mg kg-1), but the NC component was unaffected by hexamethonium (10 mg kg-1). 3. NC bronchoconstriction was reduced by morphine in a dose-dependent manner (ED50 = 132 micrograms kg-1 with a maximal inhibition of 79 +/- 2.1% at 1 mg kg-1). Yohimbine (0.5 mg kg-1) did not alter the inhibitory effect of morphine (1 mg kg-1). 4. The inhibitory effect of morphine was completely reversed by naloxone (1 mg kg-1) which had no effect on NC bronchoconstriction. Propranolol (1 mg kg-1) significantly increased the NC bronchoconstrictor response but did not significantly alter the inhibition by morphine. 5. The selective mu-opioid receptor agonist Tyr-(D-Ala)-Gly-(N-Me-Phe)-Glyol (DAGOL) was significantly more potent than morphine with an ED50 of 5.4 micrograms kg-1 and complete inhibition at 100 micrograms kg-1. The delta-agonist Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE) was less potent than DAGOL with an ED50 of 28 micrograms kg-1 and a maximal inhibition of only 50 +/- 5% at 100 micrograms kg-1. The delta-agonist Tyr4D-Pen)-Gly-Phe-D-Pen) (DPDPE) was less potent than DAGOL with an ED5o of 28pgkg-1 and a maximal inhibition of only 50 + 5% at lOOPgkg- . The Kappa-receptor agonist, U-50,488H had no inhibitory effect on the NC bronchoconstrictor response. 6. The bronchoconstrictor responses to exogenous substance P (25 pgkg- 1) or acetylcholine (25 pg kg- 1) were unaffected by morphine (500 pg kg- 1). 7. We conclude that opioids inhibit the NC bronchoconstrictor response to vagal stimulation via an action on mu-opioid receptors localized to sensory nerve endings in the airway.
 ...
PMID:Opioid modulation of non-cholinergic neural bronchoconstriction in guinea-pig in vivo. 246 5

A comparison of dopaminergic (DAergic) turnover changes in several forebrain structures was investigated after local injection of substance P (SP), neurotensin and D-Ala-Met-enkephalin (DALA) into the ventral tegmental area (VTA). A dose-dependent increase in the DOPAC/DA ratio was elicited by all 3 peptides in the nucleus accumbens and the septum. DAergic turnover was enhanced in the anteromedial prefrontal cortex only after SP injection and in the amygdala only after neurotensin injection. In the anteromedial striatum as well as in the posterolateral striatum, a significant increased DOPAC/DA ratio was observed following SP and DALA injection into the VTA. No significant changes were noticed in the olfactory tubercles after injection of the 3 peptides in the VTA. From these results, it appears that each peptide induced a different profile of DAergic activation. Taking into account the facilitatory role of the DA neurons at the level of the forebrain integrative structures, the differential activation may explain the difference in behavioral response obtained after injection of the 3 peptides in the VTA.
 ...
PMID:Substance P, neurotensin and enkephalin injections into the ventral tegmental area: comparative study on dopamine turnover in several forebrain structures. 247 75

The GRP receptor mediated growth response in Swiss 3T3 cells has been used to identify BN/GRP antagonists. Analysis of bombesin antagonism by substance P analogues and by truncated GRP analogues revealed that deletion of the C-terminal methionine residue was important for antagonism. Des-Met analogues showing potent antagonist activity in the in vitro 3T3 system (IC50 approximately 2nM) were synthesized. Further structural modification of these peptides led to the identification of (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3 (ICI 216140) which reduced bombesin-stimulated rat pancreatic amylase secretion to basal levels when administered subcutaneously at 2.0 mg per kg.
 ...
PMID:N-isobutyryl-His-Trp-Ala-Val-D-Ala-His-Leu-NHMe (ICI 216140) a potent in vivo antaconist analogue of bombesin/gastrin releasing peptide (BN/GRP) derived from the C-terminal sequence lacking the final methionine residue. 255 38


1 2 3 Next >>