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)

We studied the effects of aerosolized DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MGTA) (10(-4) M, 90 breaths), a specific inhibitor of carboxypeptidase B-type enzymes, on changes in total pulmonary resistance (RL) induced by aerosolized capsaicin (10(-7) to 10(-4) M; 10 breaths at each concentration) and vagus nerve stimulation (5 V, 5 ms, for 20 s at frequencies varying from 2 to 10 Hz) in anesthetized, atropinized, and ventilated guinea pigs. We also studied the effect of aerosolized MGTA on the bronchoconstrictor response to either aerosolized substance P, neurokinin A (10(-7) to 10(-4) M; 10 breaths at each concentration), and carbachol (10(-5) to 2 x 10(-4) M; 10 breaths at each concentration) or to i.v. administration of neurokinin A (10(-11) to 10(-8) mol/kg), bradykinin (10(-10) to 10(-7) mol/kg), and histamine (10(-8) to 10(-6) mol/kg). Although aerosolized MGTA caused no change in basal RL (P > 0.5), it did potentiate the noncholinergic bronchoconstrictor response to capsaicin (n = 5; P < 0.001) as well as to vagus nerve stimulation (n = 5; P = 0.001). In contrast, MGTA did not potentiate the bronchoconstrictor response to either aerosolized substance P, neurokinin A, and carbachol or to i.v. administration of neurokinin A, histamine, and bradykinin. Carboxypeptidase activity cleaving C-terminal arginine or lysine was found in the membrane preparations of trachea and lung from guinea pigs. The membrane-bound carboxypeptidase activity was maximal at pH 7.0 and was enhanced by the presence of CoCl2 (1 mM) in both the tracheal and lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carboxypeptidase M-like enzyme modulates the noncholinergic bronchoconstrictor response in guinea pig. 138 81

In halothane-anesthetized and -ventilated cynomologus macaque monkeys, the effects of administering vehicle (n = 3) or the neutral endopeptidase inhibitor N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (16 mg/kg, n = 5; or 100 mg/kg, n = 3, intravenously) was examined. Cisternal CSF aliquots were examined by radioimmunoassay: 1) for Met enkephalin; 2) after trypsin and carboxypeptidase B treatment for encrypted enkephalin (X-ENK); 3) for substance P; and 4) for unmetabolized drug. Similar measures were carried out in femoral artery and femoral venous plasma, except that substance P was not assayed. In CSF, prior to drug, low, but measurable levels of enkephalin (61 pg/ml), X-ENK (285 pg/ml) and substance P (16 pg/ml) were observed. Vehicle-injected animals showed no change from baseline levels over a 4-hr sampling period in either plasma or CSF levels. In contrast, following 16 mg/kg, in CSF, there was a significant 9-fold increase in MET and 11-fold increase in X-ENK at 30 min. CSF-substance P levels rose also by a factor of 2, with the peak effect observed at 60 min. All levels displayed a significant reduction by 4 hr. There was no statistical difference between the maximum effects observed with either the 16- or 100-mg/kg dose. Plasma peptide levels of enkephalin and X-ENK were not altered by drug. CSF displayed significant drug levels by 30 min, which were between 0.1 and 1% of levels observed concurrently in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of [N-(L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (SCH32615), a neutral endopeptidase (enkephalinase) inhibitor, on levels of enkephalin, encrypted enkephalins and substance P in cerebrospinal fluid and plasma of primates. 170 28

Opioid and tachykinin neuropeptides, which were derived from two biological sources (intact, and released from their corresponding precursors by the action of human cerebrospinal fluid (CSF) neuropeptidases), were characterized in human CSF by using a combination of post-high-performance liquid chromatographic (HPLC) detection techniques. Peptides were separated using gradient and isocratic reversed-phase HPLC. Radioimmunoassay measured immunoreactivity corresponding to several different individual neuropeptides including methionine enkephalin, leucine enkephalin, substance P and beta-endorphin. Commercial enzymes (trypsin, carboxypeptidase B) were used to release methionine- and leucine-enkephalin from precursors. Human CSF also served as a source of endogenous neuropeptidases. Mass spectrometry produced fragment ions that corroborated the amino acid sequence of methionine enkephalin and of substance P derived from both sources (intact, from precursors). These results demonstrated the presence of endogenous intact neuropeptides, several different neuropeptide-containing precursors and appropriate precursor-processing enzymes in human CSF for precursors of methionine enkephalin, leucine enkephalin, beta-endorphin1-31 and substance P.
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PMID:Opioid and tachykinin peptides, and their precursors and precursor-processing enzymes, in human cerebrospinal fluid. 232 43

Antisera generated to substance P-Gly (SP-G) and substance P-Gly-Lys (SP-G-K), the likely unamidated COOH-terminally extended forms of substance P, were used to quantify and localize substance P precursor forms in hamster brain stem and spinal cord. The precursor determinant SP-G-K was liberated from larger heterogeneous forms by mild trypsinization of tissue extracts and was converted into the second precursor determinant, SP-G, by subsequent treatment with carboxypeptidase B. The basal levels of SP-G-K in brain stem and spinal cord were approximately equal to 0.5 pg/mg of tissue and rose 43- to 64-fold after trypsinization. Basal levels of SP-G were comparable to those of SP-G-K and rose 10- to 29-fold after combined enzyme treatments. Immunohistochemical labeling of axons and somata with anti-SP-G-K increased dramatically after trypsinization. This labeling was eliminated by preadsorption with authentic SP-G-K but not substance P or SP-G. Gel-permeation chromatography revealed SP-G-K-like immunoreactivity in fractions corresponding to considerably higher molecular weight than mature substance P. Collectively, these results support the hypothesis that substance P is synthesized from larger precursors and demonstrate that extended precursor forms are normally present in the axons and somata of neural systems that synthesize substance P.
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PMID:Precursor forms of substance P (SP) in nervous tissue: detection with antisera to SP, SP-Gly, and SP-Gly-Lys. 241 Sep 6

Sequence analysis of bovine cDNAs has shown that the biosynthetic precursors of the tachykinins (alpha-, beta- and gamma-preprotachykinins) contain a common amino acid sequence [AYERSVMQDYERRRK] in the C-terminal flanking region. Using an antiserum raised against the synthetic peptide [YERSVMQDYE] in a specific radioimmunoassay, preprotachykinin C-terminal flanking peptide (C-PPT)-like immunoreactivity was measured in extracts of bovine corpus striatum, cerebral cortex and small intestine in concentrations that were equimolar with substance P. Consistent with the presence of two amino acid substitutions in the C-terminal flanking region of human and rat preprotachykinins, the antiserum did not detect immunoreactivity in extracts of human and rat tissues. Chromatographic analysis of the extracts identified two major immunoreactive components. It is proposed that they represent the 16-amino acid residue C-terminal flanking peptide derived from beta- and gamma-preprotachykinins and the 37-amino acid residue C-terminal flanking peptide derived from alpha-preprotachykinin. Treatment of tissue extracts with carboxypeptidase B did not result in a change in C-PPT-like immunoreactivity or in a change in chromatographic properties of the C-terminal flanking peptides suggesting that the C-terminal basic tetrapeptide (RRRK) had already been removed from the primary transcript of the preprotachykinin mRNAs by the action of endogenous processing enzymes.
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PMID:Measurement and partial characterization of the C-terminal flanking peptides from bovine preprotachykinins in extracts of brain and gut. 340 99

1 Increased vascular permeability following electric antidromic stimulation of the rat saphenous nerve was observed in the skin area supplied by the nerve, confirming previous results by other authors.2 The phenomenon was not affected by pretreatment of the rats with diphenhydramine, burimamide or their combination; atropine, methysergide, methysergide plus diphenhydramine, carboxypeptidase B, acetylsalicylic acid, indomethacin or methiazinic acid. It was partially reduced by previous injection of cellulose-sulphate, a kininogen-depleting agent.3 Perfusates from the subcutaneous tissue of the paw area supplied by the saphenous nerve contained permeability increasing activity as shown by intradermal tests in other rats. This activity was present in perfusates collected during nerve stimulation but not in those collected before stimulation. It was not destroyed by heating to 100 degrees C, or by alpha-chymotrypsin or trypsin.4 Bradykinin-like activity may appear later in the perfusates, depending on the intensity of the stimuli.5 It is concluded that following electrical antidromic stimulation of the saphenous nerve a permeability increasing factor is released, possibly from nerves. It is dialysable and can be distinguished from acetylcholine, histamine, 5-hydroxytryptamine, plasma kinins, substance P, prostaglandins and high molecular weight proteins. The increased vascular permeability induced by this factor leads to plasma exudation and activation of the kinin system.
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PMID:Formation of a factor increasing vascular permeability during electrical stimulation of the saphenous nerve in rats. 414 38