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)

Pharmacological studies were performed with neurokinin alpha and beta, new tachykinins isolated from porcine spinal cord, on smooth muscle preparations exhibiting two subtypes of substance P receptor (SP-P and SP-E receptors). The results showed that both neurokinin alpha and beta possessed the typical tachykinin activities and they exhibited SP-E-type ligand characteristics. The potency studies of SP6-11 and (Val8)SP6-11 have revealed that (VAL8)SP6-11 was comparable to SP6-11 in contracting the guinea-pig ileum (SP-P system), but greater than SP6-11 and also substance P in potentiating nerve stimulation-induced contraction of the rat vas deferens (SP-E system). The contractile response of the rat duodenum to neurokinin alpha was slow at onset and long-lasting compared with those to neurokinin beta and substance P. The residual immunoreactivity of each tachykinin in the organ bath decreased in parallel with the fading of the contractile response. The order of the half-life of each immunoreactive peptide was as follows: neurokinin alpha greater than neurokinin beta greater than substance P. The results were discussed from the viewpoints of structural significance in manifestation of pharmacological properties and in inactivation process, as well as the physiological roles of these novel mammalian tachykinins.
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PMID:Pharmacological characterization of novel mammalian tachykinins, neurokinin alpha and neurokinin beta. 608 51

The effects of perfusion through cerebral ventricles with two hexapeptides, C-terminal derivatives of substance P, on evoked tongue jerks (ETJ), were studied on male rats. During perfusion, stimulation of the infraorbital nerve caused retractive movements (ETJ) of the stretched tongue, the amplitudes of which were recorded. The mean amplitudes of ETJ recorded during each 10 min period of perfusion with McIlwain-Rodnight's solution and solution containing hexapeptides were compared. The biologically most active C-terminal hexapeptide derivative of substance P (pyro-Glu6)SP6-11, perfused through cerebral ventricles in a concentration of 5 nmol/ml increased the ETJ. This effect was dose-dependent. A 10 times higher concentration in the perfusion fluid of the less biologically active hexapeptide SP6-11 was not effective. The possibility that substance P, and its active fragments present in the fluid in cerebral ventricles, could modulate the reflex centers in the medulla is discussed.
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PMID:Influence of cerebral ventricles perfusion with hexapeptide derivatives of substance P on evoked tongue jerks in rats. 615 53

Substance P caused marked analgesic activity in rats after intraventricular administration and in mice after intraperitoneal injection. The hexapeptide pGlu6(SP6-11) was active in mice, but not in rats. Depletion of serotonin with p-chlorophenylalanine abolished the antinociceptive activity in mice, but not in rats, whereas lesion of raphe nuclei blocked the activity of substance P in the latter animals. Although different routes of administration were used, the results seem to indicate different mechanisms of analgesic activity of both peptides in rats and mice, as well as the different role of serotonergic transmission in pain control mechanisms in both species.
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PMID:Substance P, hexapeptide pGlu6(SP6-11), analgesia and serotonin depletion. 616 66

The purpose of the reported experiments was the study of the effects of intracerebroventricular (i.c.v.) administration of substance P (SP 1--11) and its hexapeptide C-terminal fragments SP 6--11 and (pGlu6)SP6--11 on the length of the estrus cycle. In the animals with a regular sequence of estrus aliquots of 250 pmol of the three peptides: SP 1--11, SP 6--11 and (pGlu6)SP 6--11 on the carier dextrane were infused into the left lateral cerebral ventricle through a chronically implanted cannula. For control, dextran solution in 0.9% NaCl was infused in a similar way. I.c.v. infusion of dextran in 0.9% NaCl, SP 1--11 and (pGlu6)SP 6--11 caused no significant changes in the length of the estrus cycle during which the infusion was done. Infusion of SP 6--11 prolonged the diestrus phase in most animals. This observation indicates that SP 6--11 exerted an effect on the hypothalamic mechanism controlling the secretion of gonadotropins by the hypophysis.
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PMID:Effect of intracerebroventricular administration of substance P and its hexapeptide fragment on the estrus cycle in female rats. 616 49

In five dogs with gastric fistulas, Heidenhain pouches, and pancreatic fistulas, the effects of substance P (SP) and its C-terminal hexapeptide (SP6-11) on gastric acid and pancreatic secretions were determined under basal conditions and in response to secretory stimulation. SP or SP6-11 infused alone in graded doses (0.25-2.0 nmol.kg-1.h-1) caused a slight but significant increase in pancreatic secretions in fasted dogs, but, when given during the secretory stimulation, they caused significant inhibition of these secretions. They reduced gastric acid response to pentagastrin and peptone meal without affecting the serum gastrin level. They caused dose-dependent inhibition of secretin-induced pancreatic bicarbonate secretion and suppressed the pancreatic protein response to caerulein, feeding, and duodenal acidification. SP6-11 was equipotent on a molar basis with SP in the inhibition of gastric or pancreatic secretion, indicating that the C-terminal portion of SP exhibits a full spectrum of the biological action of the intact molecule. The inhibitory effects of SP and SP6-11 on the stomach and pancreas were observed at a dose range that was without any significant influence on the blood pressure, indicating that they are not caused by the interference of the blood flow to the pancreas.
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PMID:Effect of substance P and its C-terminal hexapeptide on gastric and pancreatic secretion in the dog. 616 8

Repetitive stimulation of the midbrain reticular formation with electrical stimuli causes extinction of the hippocampal theta rhythm. This phenomenon was used as an indicator of the effect of intracerebroventricular administration of the C-terminal hexapeptide substance P fragment (SP6-11), Leu- and Met-enkephalin on hippocampal electrical activity in the experiments performed on rabbits. Intracerebroventricular administration of SP6-11 caused an increase in the number of trains of pulses required to produce the extinction of the theta rhythm. Both of the enkephalins had opposite effects, the effect of Met-enkephalin being more than twice as strong as Leu-enkephalin. Control administration of C-terminal pentapeptide substance P fragment (SP7-11) and 0.9% NaCl solution had no significant effect on the tested phenomenon.
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PMID:Extinction of hippocampal theta rhythm evoked by mid-brain stimulation after intracerebroventricular administration of substance P fragment and enkephalin administration in rabbits. 617 Mar 89

Effects of peptides and of acetylcholine (Ach) on electrical properties of nerve cells were compared using isolated neurons from brain of the freshwater mollusc, Lymnaea stagnalis. The peptides included certain partial sequences of Substance P (SP) and eledoisin (E). The essential C-terminal pentapeptide of eledoisin (E7-11) did not significantly influence the resting membrane potential (MP). SP hexapeptide (SP6-11) caused a dramatic depolarization. SP nonapeptide (SP3-11) had a qualitatively similar effect, but of less magnitude. Both SP6-11 and SP3-11 had a maximal effect on MP when used at a concentration of 10(-6) M. Ach also caused depolarization of the membrane, but recovery subsequent to wash-out was shorter after Ach than after peptide. Ach depolarization was blocked by d-tubocurarine chloride whereas SP6-11-induced depolarization was not antagonized. Unlike Ach, an eledoisin related peptide (EH) was found to decrease discharge rate of spontaneously discharging neurons, and whereas Ach increased membrane conductance, EH did not. These results would further suggest that Ach and these neurotropic peptides act via different mechanisms.
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PMID:Effect of substance P sequences on isolated neurons of Lymnaea stagnalis. 619 12

Substance P (SP) and its COOH-terminal fragment (6-11) were coupled to bovine serum albumin by glutaraldehyde and used to elicit antibodies. Anti-SP and anti-SP6-11 antibodies bound to the same extent 125I-[Tyr8]-SP and 125I-[T-Lys6]-SP6-11. The latter was obtained after conjugation of the [Lys6]-SP6-11 with cold Bolton-Hunter reagent and then labelling by the chloramine-T method. In contrast to 125I-[Tyr8]-SP, 125I-[Tyr8]-SP6-11 was poorly bound by both anti-SP and anti-SP6-11 antibodies. Synthetic fragments of SP shorter than SP7-11 did not react with anti-SP6-11 antibodies. It is concluded that the antigenic determinant is within the COOH-terminal pentapeptide, and that Phe7, Phe8, Leu10 and Met11 contribute significantly to both anti-SP and anti-SP6-11 immunoreactivity.
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PMID:Immunogenic and antigenic properties of the COOH-terminal hexapeptide of substance P. 620 58

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

A series of analogues of the previously reported NK1 tachykinin antagonist [Orn6, Glu(OBzl)11]-SP6-11-OBzl has been synthesized and tested in order to investigate the effects on antagonistic activity of modifications at the C-terminal residue. The biological activity in the guinea-pig ileum assay (NK1 receptor) indicates that the two aromatic rings introduced in the C-terminal part of the peptide are both essential for the expression of antagonistic activity.
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PMID:Synthesis and biological activity of NK1 tachykinin antagonists not containing D-residues. 751 97


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