Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Post-proline endopeptidase (PPE, EC 3.4.21.26) was purified 3,450 times from human lung. PPE was routinely assayed with the artificial substrate, carbobenzoxy-glycyl-L-prolyl-p-nitroanilide (Z-Gly-Pro-pNA). The pH optimum was 7.4, and the Mr was 77,000. Thiol blocking agents were strongly inhibitory but serine blocking agents were not inhibitory. No metal ions were required for activity, but heavy metal ions such as Hg2+, Cu2+, Cd2+, and Zn2+ completely inactivated the enzyme. Both dithiothreitol (DTT) and ethylenediaminetetraacetic acid (EDTA) were required to stabilize PPE activity. Michaelis constant values for Z-Gly-Pro-pNA and carbobenzoxy-glycyl-L-prolyl-2-naphthylamide were 0.36 and 0.10 mmol/l, respectively. PPE cleaved vasoactive peptides including bradykinin (BK) and des-(Arg9)-BK (Pro3-Gly4 and Pro7-Phe8 bonds), angiotensins I and II (Pro7-Phe8 bond), substance P (Pro4-Gln5 bond), and oxytocin (Pro7-Leu8 bond). Each of these peptides inhibited PPE-catalyzed hydrolysis of Z-Gly-Pro-pNA competitively. BK had the lowest Ki value (2.35 mumol/l) and oxytocin had the highest Ki value (84.0 mumol/l). PPE was not inhibited by captopril, a potent inhibitor of angiotensin converting enzyme, which also cleaves the Pro7-Phe8 bond of BK.
 ...
PMID:Human lung post-proline endopeptidase: purification and action on vasoactive peptides. 354 26

The effect of four semi-purified compounds obtained from Mandevilla velutina crude extract by silica gel chromatography fractionization were analysed for their inhibitory effects on uterine contractions induced by bradykinin (BK), lysylbradykinin (L-BK), acetylcholine (ACh) and oxytocin, in vitro. None of the compounds tested affected uterine tone. Pre-incubation for 20 min with fraction 12 (20 to 80 micrograms ml-1), isolated from M. velutina produced a parallel and concentration-dependent displacement to the right of the concentration-response curves for BK and L-BK (1 to 1000 nM). Schild plots of these data were linear (correlation close to unity) and yielded a nominal pA2 value (as g ml-1) of 5.1 and 4.9, respectively, and the values of the slopes were not significantly different from unity. Fraction 11 (10 to 40 micrograms ml-1) also produced a parallel and concentration-dependent displacement to the right of the BK concentration-response curve. The Schild plot gave a mean pA2 value (g ml-1) of 5.4 and a slope not significantly different from unity. Fraction 12 did not influence the uterine contractile responses induced by ACh (0.1 to 100 microM) and oxytocin (0.01 to 30 miu ml-1) at concentrations less than 80 micrograms ml-1. Fraction 16 (20 to 80 micrograms ml-1) antagonized the action of BK only at concentrations greater than 40 micrograms ml-1, whereas fraction 5 (20 to 80 micrograms ml-1) was completely inactive against BK-induced responses. 5 As observed previously with the crude extract, the onset of the BK antagonistic action of these compounds was rapid and completely reversible following intermittent washing of the preparation for 30-60 min. 6 These results indicate the existence of at least two compounds in the crude extract of Mandevilla velutina that act as competitive and selective kinin antagonists on the isolated uterus of the rat.
 ...
PMID:Kinin antagonist activity of compounds from Mandevilla velutina in the rat isolated uterus. 359 76

A low concentration (0.2 nM) of oxytocin induced phasic tension development in the isolated uterus of the day-22 pregnant rat. Tonic spasm was also induced by higher concentrations of oxytocin (2 and 20 nM). Spasmogenic responses to bradykinin and potassium chloride (KCl) also contained phasic and tonic components while acetylcholine induced tonic spasm only. The phasic component of the responses to oxytocin and to bradykinin and both components of the response to KCl were inhibited by (+)-cis diltiazem (0.1 and 1 microM). The tonic component of the responses to oxytocin and to bradykinin and the responses to acetylcholine were only reduced by (+)-cis diltiazem at concentrations greater than 10 microM. (-)-cis Diltiazem was less potent than (+)-cis diltiazem as an inhibitor of calcium (Ca2+)-induced spasm in a depolarizing medium and of the phasic spasms induced by oxytocin. The two isomers were of similar potency as inhibitors of oxytocin-induced tonic spasm. Spasmogenic responses to oxytocin, bradykinin, acetylcholine and KCl were decreased when uteri were bathed in media which were Ca2+-free or of low Na+ content. However, there was no correlation between the rank order of sensitivity of the four spasmogens to the changed media and to their inhibition by (+)-cis diltiazem. Oxytocin (0.2 nM) increased the frequency, duration and amplitude of spike activity, measured by extracellular electrical recording, in parallel with enhancement of phasic tension development. With higher concentrations of oxytocin (2 and 20 nM) spike firing was initially continuous but often subsequently ceased despite the associated tonic contracture. After incubation in (+)-cis diltiazem (10 microM), oxytocin (0.2, 2 and 20 nM) produced graded tonic spasm without spike activity. Oxytocin (0.2 nM) produced a small increase in 45Ca2+ influx into myometrium as assessed by the 'lanthanum method'. Higher concentrations of oxytocin (2 and 20 nM) did not increase 45Ca2+ influx. It is concluded that the phasic component of the response of the uterus to oxytocin and bradykinin is associated with Ca2+ influx via voltage-dependent Ca2+ channels. The tonic component is due to another mechanism(s) which does not appear to involve Ca2+ influx. All of the spasmogenic response to KCl can be explained by Ca2+ influx through voltage-dependent Ca2+ channels. These channels do not appear to be involved in the spasmogenic response to acetylcholine.
 ...
PMID:The spasmogenic action of oxytocin in the rat uterus--comparison with other agonists. 374 62

These studies were initiated to examine the effects of indomethacin on uterine contractile responses to oxytocin, carbachol, bradykinin, angiotension II and isoproterenol. Isolated uterine horns used in this study were removed from immature (21 days old) ovariectomized Sprague-Dawley rats (40-50 gm). Pre-treatment of uterine horns with indomethacin (10(-3) M) for periods of 15,30,60,90, and 180 seconds resulted in maximal inhibition of oxytocin-induced contractions by 15 seconds. In an indomethacin dose-response study, oxytocin-induced contractions were completely eliminated by a dose of indomethacin of 10(-3) M. Utilizing doses of indomethacin (3.5 X 10(-4) and 5.0 X 10(-4) M) that significantly reduced oxytocin-induced contractions by 48 and 77% respectively, contractile responses induced by carbachol (10(-6) M), bradykinin (10(-6) M), and angiotension II (4 X 10(-11) M) were not significantly reduced. Relaxation of uterine smooth muscle by isoproterenol (10(-5) M) in the presence of carbachol (10(-5) M) was not altered by indomethacin pretreatment. Data from this study demonstrate that indomethacin selectively inhibits oxytocin-induced uterine contractions in the immature rat.
 ...
PMID:The selective effects of indomethacin on contractile responses of the isolated rat uterus. 378 May 98

Various agonists induced sustained contractions of estrogen-dominated rat uterine smooth muscle in Ca-free salt solution containing 0.2 mM EGTA after incubation of the muscle with 3 mM EGTA for 1 hr. The magnitudes of contraction varied with agonists. (bradykinin greater than oxytocin greater than or equal to vasopressin greater than PGF2 alpha greater than angiotensin II greater than acetylcholine greater than or equal to PGE2 greater than or equal to 5-hydroxytryptamine. Addition of 10(-4) Ca ion reduced the tension developed: Ca ion inhibited these contractions when they were sufficiently large (marked inhibition on bradykinin-, oxytocin-, and vasopressin-induced contractions; definite one on PGF2 alpha-induced contraction), as observed previously with oxytocin-induced contraction under the same conditions and named "Ca Reversal".
 ...
PMID:Calcium reversal: inhibition by Ca ion of sustained contraction in Ca-free medium induced by various agonists in rat uterine smooth muscle. 392 49

Peptides and non-peptides acting as vasoconstrictors or vasodilators have been tested in dog isolated carotid arteries with and without endothelium and in the presence and absence of a variety of antagonists and inhibitors of endogenous substances. It has been found that substance P and several other tachykinins, bradykinin, neurotensin, bombesin and acetylcholine relax the isolated artery only when the endothelium is present, while VIP, isopropylnoradrenaline, adenosine, histamine, prostaglandins E1 and E2, glucagon and insulin relax and angiotensin, vasopressin, oxytocin, 5-HT and noradrenaline contract the isolated vessel, no matter whether the endothelium is present or not. Peptide and non-peptide antagonists have been used with success to show that vasoconstrictors and vasodilators act on specific receptors, since their effects are reduced in the presence of antagonists, specific for one or another of the various agents. Inhibitors of the arachidonic acid cascade only reduce the effect of acetylcholine, suggesting that at least two different mechanisms are involved in the endothelium-mediated relaxation of arterial smooth muscles to peptide and non-peptide agents. The results summarised in this paper suggest that the site of action of several vasodilators is the endothelium, while other vasodilators and all the vasoconstrictors influence the arterial vessels tone presumably by acting on the smooth muscle cells.
 ...
PMID:Effects of peptides and non-peptides on isolated arterial smooth muscles: role of endothelium. 393 Feb 67

A crude aqueous alcoholic extract of Mandevilla velutina (Apocynaceae) rhizomes produced a concentration-dependent displacement to the right of the concentration-response curve to bradykinin (Bk) in the isolated uterus of the rat. Schild analysis of the data revealed a linear relationship (r = 0.99) and yielded a pA2 value of 3.3 + 0.08 (- log g ml-1) but the slope differed significantly from unity. The anti-Bk action was of rapid onset and was reversible upon washout. Contractions induced by acetylcholine, oxytocin, angiotensin II and BaCl2 were unaffected by the extract. This represents the first report of a selective Bk antagonist of plant origin. The isolation of the active principle(s) may result in a useful pharmacological tool for elucidating the physiological and physiopathological roles of endogenous Bk.
 ...
PMID:The selective antagonism of bradykinin action on rat isolated uterus by crude Mandevilla velutina extract. 404 75

Short-latency emetic responses were induced in dogs by injecting angiotensin II (AII), arginine vasopressin (AVP), and neurotensin (NTN) into cerebroventricular (ICV) and cisternal (ICT) sites also responsive to the emetic effects of apomorphine (APO). Angiotensin III, bradykinin, bombesin, oxytocin, adrenocorticotropic hormone, substance P, gastrin-related peptide and cholecystokinin were ineffective. The results suggest a possible dopaminergic mediation of peptide-induced emesis by receptors in the area postrema (AP).
 ...
PMID:Emetic effects of centrally administered angiotensin II, arginine vasopressin and neurotensin in the dog. 404 79

The survival of adult rat hepatocytes in monolayer culture was studied in the presence of different hormones (neurotensin, oxytocin, thyrotropin releasing hormone, luteinizing hormone releasing hormone, cholecalciferol, bradykinin, substance P, aldosterone, melanocyte stimulating hormone, 3,3',5-triiodo-1-thyronine, corticosterone, human growth hormone, glucagon, insulin, progesterone, testosterone, estradiol, and dexamethasone phosphate) or growth factors (fetal bovine serum). For this purpose trypan blue exclusion, lactate dehydrogenase, and DNA and protein content were measured at 24 and 72 h of culture. 10(-7) M Dexamethasone, a mixture of eight hormones, 10% fetal bovine serum, and a combination of the latter two supplements caused a more than 64% higher DNA content at 72 h when compared to control cultures. A striking agreement of these results with changes of lactate dehydrogenase leakage was observed, whereas trypan blue exclusion gave erratic results. Considerable changes of cell arrangement apparently specific for each supplement were observed by low magnification microscopy. It is concluded that glucocorticoids and fetal bovine serum have an outstanding effect on cell viability and that DNA or protein content or both are reliable indicators of cell viability in amitotic cultures.
 ...
PMID:Influence of hormones and growth factors on viability, DNA, and protein content of adult hepatocytes in primary culture. 405 11

The effect of (+) IPNEA on various stimulant drugs was examined on isolated rat uterus. Addition of (+) IPNEA (1 times 10- minus 5 g/ml) to the organ bath, produced marked potentiation in the contractile responses of oxytocin and prostaglandins. Potentiation was less significant to 5-HT, vasopressin, angiotensin and bradykinin. (+) INPEA did not potentiate the responses of oxytocin on isolated rat mammary strip and the responses of prostaglandins on rat stomach (fundus) strip, guinea-pig tracheal chain and guinea-pig ileum. The significance of these findings has been discussed.
 ...
PMID:Potentiation of oxytocin and prostaglandins-evoked responses by (+) INPEA on isolated rat uterus: its specificity and selectivity. 415 75


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