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)

Substance P (SP) and an analogue (Lys-Phe-Ile-Gly-Leu-MetNH2 = EH) were tested in acute experiments on the blood pressure in the intact rat anaesthetized with urethane. A biphasic response, consisting of an initial depressor, followed by a pressor component, was seen. In low concentrations, SP decreases blood pressure, in medium concentrations SP produces a pronounced biphasic response, in high concentrations SP produces only hypertensive reactions. In chronic experiments, SP-peptides act also in different directions. After EH, disorders in avoidance learning were completely eliminated from 10 weeks old spontaneously hypertensive rats (SHR) or conditionally from SHR age 14 or 26 weeks. Elevated blood pressure in SHR aged 26 weeks was reduced by EH. Blood pressure in SHR aged 14 weeks was almost unaffected by EH and blood pressure went up in ten weeks old SHR. SP had a weaker action in comparison with EH. These results are in agreement with the hypothesis proposed by Oehme and co-workers [11-13] that SP can act as a regulatory peptide (="regulide").
 ...
PMID:Action of substance P and an analogue on blood pressure and avoidance learning in rats with spontaneous hypertension (SHR). 616 97

The effects of Substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2) and of a SP hexapeptide analogue (SP-A) (Lys-Phe-Ile-Gly-Leu-MetNH2) on active avoidance learning were investigated in spontaneously hypertensive rats (SHR) and Wistar rats. Active avoidance learning was slower in SHR than in Wistar rats. SP-A "normalized" the slower active avoidance learning in SHR, whereas SP did not. Some possible causes of this difference as well as the mechanism of the normalizing effect of SP-A are discussed.
 ...
PMID:Action of substance P and an SP-hexapeptide analogue on avoidance learning in rats. 618 27

The tissue content of up to eight neuropeptides, viz bombesin (BOM), cholecystokinin (CCK-8), neurotensin (NT), neuropeptide Y (NPY), peptide histidine isoleucine amide (PHI), somatostatin (SRIF), substance P (SP) and vasoactive intestinal polypeptide (VIP), in rat hypothalami removed at various times of the day, was measured using specific radioimmunoassays. There was significant variation in the content of BOM, CCK-8, NT, PHI, SP and VIP across a 24-h period. The levels of BOM, CCK-8 and NT were lowest around the onset of darkness (1900 h) and rose throughout the night to reach a peak around the time of lights on. Hypothalamic content of all eight peptides fell between 0700 h and 1300 h by an average of 45 +/- 4%. Basal release of these peptides, as well as that in the presence of 48 mM potassium (K+), was measured from hypothalami removed between 0700 and 1900 h and incubated in vitro in a CSF-like medium. Basal secretion of NT significantly increased, whilst that of CCK-8 significantly decreased over the same period. There was no significant change in the basal release of the other neuropeptides. The release in the presence of 48 mM K+ of SP decreased significantly during the day, whilst that of VIP significantly increased. There was also a significant change in the stimulated release of BOM, levels falling during the morning and rising again at 1900 h. 48 mM K+ caused a significant increase in the release of SRIF and SP at all times tested. Whilst 48 mM K+ induced a significantly higher release of CCK-8 and NT in the morning, this stimulus was ineffective in the evening. The contrary was true in the case of BOM, NPY and VIP, where a significant stimulation was induced only at 1900 h. The possible implications of these findings are discussed.
 ...
PMID:24-hour variation in content and release of hypothalamic neuropeptides in the rat. 619 15

Enteroendocrine cells containing glucagon-, substance P-, neurotensin- and VIP-like substances have been demonstrated immunocytochemically in the gut of Barbus conchonius. Mainly based on the distribution of the immunoreactive endocrine cells in this and a previous study, at least eight different enteroendocrine cell types appear to be present in this stomachless fish: C-terminal-gastrin-immunoreactive cells, predominantly present in the upper parts of the folds of the proximal part of the intestinal bulb. Metenkephalin-immunoreactive cells, basally located in the folds of the first segment. Pancreatic polypeptide (PP)-immunoreactive cells, mainly present in the first half of the first segment. Glucagon-like-immunoreactive (GLI) cells that are basally located in the folds of the first segment and that contain a different polypeptide (possibly glicentin) than pancreatic glucagon cells. Substance P-immunoreactive cells, present in the upper parts of the folds throughout the gut. C-terminal-neurotensin-immunoreactive cells, basally located in the folds throughout the first segment. Vasoactive intestinal polypeptide (VIP)-immunoreactive cells, present in small numbers in the proximal part of the intestinal bulb. Nonspecifically-immunoreactive cells, found throughout the intestinal bulb. Many VIP-immunoreactive nerves have been demonstrated in the smooth muscle layer and myenteric plexus of the gut; furthermore some of them are peptide histidine-isoleucine (PHI)-immunoreactive. Substance P-, somatostatin-, neurotensin- and met-enkephalin-immunoreactive nerves are also found. Thus, at least partial sequences of four different mammalian neuropeptide hormones (VIP, substance P, neurotensin, met-enkephalin) occur both in endocrine cells and enteric nerves of the gut of B. conchonius.
 ...
PMID:Immunohistochemical localization of (neuro)peptide hormones in endocrine cells and nerves of the gut of a stomachless teleost fish, Barbus conchonius (Cyprinidae). 620 50

Nerves containing immunoreactive vasoactive intestinal polypeptide (VIP), substance P and two newly discovered peptides, neuropeptide tyrosine (NPY) and PHI (peptide having N-terminal histidine and C-terminal isoleucine), have been found in the human urinary bladder by immunocytochemistry and radioimmunoassay. Somatostatin immunoreactivity was detected by radioimmunoassay. The VIP-immunoreactive nerves were widely distributed in all regions, but were particularly dense beneath the epithelium and in the muscle layer. Scattered intramural ganglia were found to be reactive to VIP antiserum. Higher concentrations of extractable VIP were detected in the trigone than in the dome. VIP- and PHI-immunoreactive nerves were similarly distributed, the latter being less numerous. NPY-immunoreactive nerves were seen mainly in the muscle layer, particularly in the trigonal area. The distribution patterns of VIP- and NPY-immunoreactive nerves resembled those of the previously reported cholinergic and adrenergic nerves, respectively. Many blood vessels were found to be innervated by both types of immunoreactive nerves. Scattered substance P-immunoreactive fibers were occasionally seen, being present in the submucosa and around the detrusor muscles. The significance of these nerves remains to be elucidated.
 ...
PMID:Peptide-containing nerves in human urinary bladder. 620 53

A shortened and modified eledoisin-hexapeptide sequence (Lys-Phe-Ile-Gly-Leu-MetNH2) was tested for their action on avoidance learning and blood pressure of rats with spontaneous hypertension (SH-rats) and intact Wistar rats. Both groups were 10, 14, and 26 weeks of age. Disorders of avoidance learning and elevation of blood pressure were likely to aggravate along with growing age of SH-rat. The used eledoisin-hexapeptide sequence is related to the essential C-terminal pentapeptide sequence of Substance P (SP). After injection of the used hexapeptide at doses of 250 microgram/kg intraperitoneally disorders in avoidance learning were completely eliminated from ten-week SH-rats or conditionally for SH-rats aged 14 and 26 weeks. Elevated blood pressure in SH-rats aged 26 weeks was reduced by the hexapeptide from 220 Torr to approximately 190 Torr. Blood pressure in SH-rats aged 14 weeks, originally about 180 Torr, was almost unaffected by the hexapeptide. Blood pressure went up from about 150 Torr to 190 in ten-week-old Sh-rats. A hypothesis was made about the mode of action of Substance P and related peptides.
 ...
PMID:Effects of a substance P-analogue on blood pressure and avoidance learning of rats with spontaneous hypertension. 728 83

1 The stimulatory effects of neurotensin (NT) and several NT fragments were evaluated in two pharmacological preparations: rat stomach strips and isolated spontaneously beating atria of guinea-pigs.2 In rat stomach strips, NT elicited a dose-dependent contractile effect in concentrations varying between 1.3 x 10(-9) and 5.4 x 10(-7) M.3 The contractile effect of NT (1.3 and 5.4 x 10(-8) M) in this tissue was not modified by atropine (3.4 x 10(-7) M), methysergide (2.0 x 10(-6) M), a mixture of cimetidine (8.0 x 10(-6) M) and diphenhydramine (7.8 x 10(-6) M), indomethacin (1.4 x 10(-5) M), 8-Leu-angiotensin II (1.0 x 10(-6) M), glucagon (2.0 x 10(-6) M) or somatostatin (3.0 x 10(-7) M).4 Rat stomach strips desensitized by bradykinin (6.1 x 10(-6) M) or substance P (7.4 x 10(-6) M) maintained their sensitivities to NT (1.3 and 5.4 x 10(-8) M).5 In guinea-pig atria, NT produced a dose-dependent positive inotropic action in concentrations varying between 5.4 x 10(-10) and 2.7 x 10(-7) M.6 The inotropic effect of NT (2.7 x 10(-9) M) was not influenced by methysergide (2.8 x 10(-6) M), atropine (3.4 x 10(-7) M), practolol (1.5 x 10(-5) M), 8-Leu-angiotensin II (1.0 x 10(-6) M), or indomethacin (1.4 x 10(-5) M), but it was reduced by 37% by cimetidine (4.0 x 10(-5) and 2.0 x 10(-4) M). A combination of cimetidine (4.0 x 10(-5) M) and diphenhydramine (3.9 x 10(-6) M) did not produce a greater inhibition of NT than cimetidine alone.7 Atria desensitized by bradykinin (6.1 x 10(-6) M) or glucagon (2.0 x 10(-6) M) maintained their sensitivities to NT (2.7 x 10(-9) M). Substance P was inactive both as an agonist or antagonist of NT.8 These results suggest the existence of specific NT receptors in rat stomach strips and guinea-pig atria.9 The data derived from our structure-activity study suggest that the minimum structure required for the full stimulation of NT receptors in these two preparations is H-Arg(9)-Pro(10)-Tyr(11)-Ile(12)-Leu(13)-OH. The sequence PyroGlu(1)-Leu(2)-Tyr(3)-Glu(4)-Asn(5)-Lys(6)-Pro(7)-Arg(8)- and the amino acids Ile(12) and Leu(13) appear to contribute mainly to the affinity or binding of NT to its receptor. The chemical groups responsible for the full activation (intrinsic activity) of NT receptors seem to be located in the sequence -Arg(9)-Pro(10)-Tyr(11).
 ...
PMID:The stimulatory effects of neurotensin and related peptides in rat stomach strips and guinea-pig atria. 735 2

The injection of 250 microgram/kg SP-analogue (Lys-Phe-Ile-Gly-Leu-MetNH2) is able to restore the reduced or disturbed delta activities and paradoxical sleep periods of the sleeping EEG in chronically stressed rats. Thus it has been proved that Substance P, which we would like to term as an ,,regulatory peptide" (equal to regulide) has a modulating function.
 ...
PMID:[Effect of a substance P analog on sleep deprivation]. 742 32

The immunosuppressive activity of three pentapeptides related to the C-terminal fragments of tachykinins was investigated using the PFC (plaque forming cell) test. The peptides were of the general structure Phe-X-Gly-Leu-Met-NH2, with Tyr, Val and Ile in X position, respectively. The results were compared with those obtained previously for the substance P (SP) C-terminal pentapeptide. It was found that peptides containing aromatic residues in X position were more potent immunosuppressors than peptides containing aliphatic residues in the same position. The results also suggest that in mammalian organisms substance SP may be involved in immunomodulation which is rather not the case with other mammalian tachykinins (neurokinin A and neurokinin B).
 ...
PMID:Immunosuppressive activity of C-terminal fragments of tachykinins. 748 53

During evolution mutations have occurred in peptide receptors that are neutral with respect to binding of the natural peptide ligand but frequently affect the binding of nonpeptide antagonists. By systematically introducing the nonconserved residues from the human neurokinin (NK)-1 receptor into the corresponding rat receptor we have attempted to localize the structural elements that are responsible for 15-76-fold higher affinity of three tachykinin nonpeptide antagonists for the human receptor, compared with the corresponding rat receptor. Surprisingly, exchange of the four divergent residues located around the previously located apparent binding site for CP 96,345 and FK 888 at the top of transmembrane segment (TM) V and VI, either alone or as a group, did not affect the binding of these nonpeptide compounds. However, substitution of Ser290 in TM VII of the rat receptor with isoleucine present in the human receptor increased the affinity for FK 888 20-fold and that for CP 96345 6-fold, corresponding to an affinity that was only about 4-fold less than the affinity for the human NK-1 receptor. Full human-like affinity for FK 888 and CP 96,345 could be conveyed to the rat receptor by the combined substitution of Ser290 in TM VII to isoleucine and Leu116 in TM III to valine. The NK-2 receptor-selective compound SR 48,968 was found to bind with low affinity to the human NK-1 receptor but with 15-fold even lower affinity to the rat receptor. Substitution of residue 290, which is situated within the previously located binding site for this compound, could completely account for this difference. These data demonstrate that the species selectivities of the nonpeptide antagonists CP 96345, FK 888, and SR 48,968, independently of clear differences in their chemical structures and modes of discovery, have a similar structural basis, being dependent on two divergent residues that apparently are not involved in peptide agonist binding.
 ...
PMID:The species selectivity of chemically distinct tachykinin nonpeptide antagonists is dependent on common divergent residues of the rat and human neurokinin-1 receptors. 750 41


<< Previous 1 2 3 4 5 6 7 8 9 10