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

The endopeptidase, post-proline cleaving enzyme, has been purified 10,500-fold in an overall yield of 18% from lamb kidney. The enzyme possesses a specific activity of 45 mumol/mg/min as tested with the substrate Z-Gly-Pro-Leu-Gly (Km = 6.0 X 10(-5)), has a molecular weight of 115,000, is comprised of two subunits with a molecular weight of 57,000, and exhibits maximal activity at pH 7.5 to 8.0. With the exception of the -Pro-Pro linkage, the -Pro-X-peptide bond (X equals L- and D-amino acid residues) located internally in the peptide sequence can be hydrolyzed (cleavage occurs faster when X = lipophilic side chain as compared to X = acidic side chain). The appropriate -Pro-X- bonds in zinc-free porcine insulin, oxytocin, arginine vasopressin, angiotensin II, bradykinin-potentiating factor were cleaved. Human gastrin, adrenocorticotropic hormone, denatured guinea pig skin collagen, and ascaris cuticle collagen were not degraded. Dipeptides with the structure Z-Pro-LD-X competitively inhibit post-proline cleaving enzyme.
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PMID:Post-proline cleaving enzyme. Purification of this endopeptidase by affinity chromatography. 1 73

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
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PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

An enzyme which catalyzes the deamidation of thyroliberin (TRF; less than Glu-His-Pro-NH2) has been purified 110-fold from extracts of bovine anterior pituitary by ammonium sulfate fractionation, ion exchange chromatography on DEAE-cellulose, and gel filtration. This enzyme of 76,000 molecular weight (as estimated by gel filtration) exhibits maximal activity at neutral pH (optimum pH 7.4 to 7.6) in buffers of high ionic strength supplemented with thiol-protecting agents. As indicated by the strong inhibition of the enzymatic activity by N-ethylmaleimide and Hg2+, as well as by the extreme sensitivity toward diisopropyl fluorophosphate, -SH, and -OH residues apparently represent essential functional groups of the enzyme. The stereospecific deamidation of TRF (Km = 4.1 . 10(-4) M) is inhibited competitively by TRF analogues which contain proline or by the proline containing biologically active peptides luliberin (LH-RF), oxytocin, vasopressin, angiotensin II, and Substance P. TRF analogues without proline or peptide amides without proline are ineffective. This enzyme cleaves the appropriate Pro-X bonds in luliberin, angiotensin II, pyroGlu-His-Pro-Gly-NH2, and the collagenase substrate Z-Gly-Pro-Leu-Gly-Pro. Thus, it may be characterized as a post-proline-cleaving enzyme.
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PMID:Characterization of "thyroliberin-deamidating enzyme" as a post-proline-cleaving enzyme. Partial purification and enzyme-chemical analysis of the enzyme from anterior pituitary tissue. 11 64

Production, transport, storage and release of antidiuretic hormone (ADH) in the hypothalamo-neurohypophysial system were investigated. ADH produced by nerve cells in the paraventricular and supraoptic nuclei of the hypothalamus is present in a form bound to the specific protein neurophysin, in the neurosecretary granula. Electric and chemical stimulation of these nuclei results in evoked release of ADH in ionic association with neurophysin from the neural lobes. Acetylcholine, norepinephrine, histamine, angiotensin II, gamma-aminobutyric acid and L-glutamic acid have been regarded as candidates of chemical transmitters for the release of ADH in the hypothalamus. Prostaglandin (PG) E2 may be another important compound for central regulation of water metabolism. The possibility that PGE2 may be the transmitter or a modulator in the nuclei has to be considred. Serotonin, dopamine and taurine, however, may not be involded in the ADH releasing mechanisms in the hypothalamus. It appears that norepinephrine, histamine, angiotensin II, PGE2 and bradykinin stimulate directly the neural lobe to release ADH. The ADH release is regulated by intracellular Ca++. The existence of a "readily-releasable pool" of ADH can be ruled out and any limitation in the amount of ADH released under experimental conditions may be due to insufficient activation of the neural lobe. A physiological significance other than a carrier was proposed for neurophysin.
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PMID:[The hypothalamo-neurohypophysial system and antidiuretic hormone (author's transl)]. 33 45

1. Intracranial injections of the individual components of the renin-angiotensin system caused drinking in water-replete dogs. 2. Angiotensin II was the most reliable, potent and rapidly acting intracranial dipsogen and elicited drinking in the absence of peripheral circulatory changes. After the highest dose of angiotensin II (10(-9) mole) five dogs drank a mean amount of 380.0 +/- 88.6 ml. For the other components, the order of dipsogenic effectiveness was angiotensin I, synthetic renin substrate, and angiotensin III. 3. Isotonic saline, bradykinin (10(-10) mole), eledosin-hexapeptide (10(-10) mole), oxytocin (10(-10) mole) and prostaglandin F2alpha (1-200 X 10(-12) mole) were ineffective. 4. Intracranial renin (10 m-u.) produced a mean intake of 445 +/- 152 ml. of water in eight dogs. 5. Dog renin substrate and synthetic renin substrate, injected intracranially in a dose of 10(-10) mole, produced similar intakes of water but these amounts were very much less than the volume drunk in response to the same dose of angiotensin II. 6. None of the components injected into dipsogenically responsive sites in the brain caused changes in blood pressure, although the act of drinking itself produced a small rise. 7. Angiotensin II at the highest dose produced drinking when injected into the subfornical organ, preoptic region, anterior hypothalamus, lateral ventricle, third ventricle, ventral hippocampus and mid-line thalamus. Negative sites were found in the caudate nucleus, fourth ventricle, mid-brain, posterior thalamus, dorsal hippocampus, lateral hypothalamus and posterior hypothalamus. 8. After the lowest dose of intracranial angiotensin II (10(-12) mole) only the preoptic region and subfornical orgal were responsive. These two sites were equally sensitive in terms of latency and amounts drunk at all doses injected. 9. Angiotensin did not necessarily have to reach a cerebral ventricle in order to cause drinking. 10. The dog resembles the rat in its responsiveness to the dipsogenic action of intracranial angiotensin II. The regions of the brain from which drinking can be elicited are more widespread than has been claimed by some in the rat.
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PMID:Drinking and haemodynamic changes induced in the dog by intracranial injection of components of the renin-angiotensin system. 65 Apr 66

1. The hormonal control of glycogen breakdown was studied in hepatocytes isolated from livers of fed rats. 2. Glucose release was stimulated by [8-arginine]vasopressin (10pm-10nm), oxytocin (1nm-1mum), and angiotensin II (1nm-0.1mum). These responses are all at least as sensitive to hormone as is glucose output in the perfused rat liver. 3. The effect of these three hormones on glucose release was critically dependent on extracellular Ca(2+), unlike that of glucagon. Half-maximal restoration of the vasopressin response occurred if 0.3mm-Ca(2+) was added back to the incubation medium. 4. Glycogen breakdown was more than sufficient to account for the glucose released into the medium, in the absence or presence of hormones. Lactate release by hepatocytes was not affected by vasopressin, but was inhibited by glucagon. 5. If Ca(2+) was omitted from the extracellular medium, vasopressin stimulated glycogenolysis, but not glucose release. 6. The phosphorylase a content of hepatocytes was increased by vasopressin, oxytocin and angiotensin II; minimum effective concentrations were 0.1pm, 0.1nm and 10pm respectively. This response was also dependent on Ca(2+). 7. These results demonstrate that hepatocytes can respond to low concentrations of vasopressin and angiotensin II, i.e. these effects are likely to be relevant in the intact animal. The role of extracellular Ca(2+) in the effects of these hormones on hepatic glycogenolysis and glucose release is discussed.
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PMID:Rapid stimulation by vasopressin, oxytocin and angiotensin II of glycogen degradation in hepatocyte suspensions. 66 48

1. In hepatocytes from starved rats, vasopressin, angiotensin (angiotensin II) and oxytocin stimulated gluconeogenesis from lactate by 25--50%; minimal effective concentrations were about 0.02pM, 1 nM and 0.2 nM respectively. 2. Vasopressin and angiotensin also stimulated gluconeogenesis from alanine, pyruvate, serine and glycerol. EGTA decreased gluconeogenesis from these substrates. 3. Hormonal stimulation of gluconeogenesis from lactate was abolished in the absence of extracellular Ca2+. 4. Insulin did not prevent stimulation of gluconeogenesis by vasopressin or angiotensin. 5. The potency of the stimulatory effects of vasopressin and angiotensin on hepatic gluconeogenesis suggests they are operative in vivo. Also, the data suggest that Ca2+ plays a role in the stimulation by these hormones.
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PMID:Stimulation by vasopressin, angiotensin and oxytocin of gluconeogenesis in hepatocyte suspensions. 74 59

Tissue factor apoprotein and relipidated tissue factor preparations extensively hydrolyze bradykinin, Lys-bradykinin, Met-Lys-bradykinin, substance P, [Asp1, Ile5]-angiotensin II, [Asp1, Ile5]-angiotensin I, and human fibrinopeptide A while acting more slowly on [Sar1, Ile5]-angiotensin II, [Me2Gly1, Ile5]-angiotensin II, bradykinin potentiating pentapeptide from B. jararaca, luteinizing hormone-releasing hormone, melanocyte stimulating hormone-release-inhibiting factor (Pro-Leu-Gly-NH2), and oxytocin. No hydrolysis of thyrotropin-releasing factor or bradykinin potentiating nonapeptide from B. jararaca is observed. Relipidated and apoprotein tissue factor act at identical rates under the conditions of the assay. Dansylation and chromatography of tissue factor-peptide incubation mixtures further indicate that relipidated and apoprotein tissue factor also hydrolyze peptides by identical mechanisms. No fewer than six bonds are hydrolyzed in bradykinin while the angiotensins and substance P are degraded to constituent amino acids. Only the N-terminal alanine is released from fibrinopeptide A. 2-Mercaptoethanol greatly inhibits the hydrolysis of bradykinin by relipidated tissue factor.
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PMID:The hydrolysis of biologically active peptides by bovine lung tissue factor (thromboplastin). 78 91

In order to study renal tubular handling of two small peptide hormones, [14c]angiotensin II ([14C]AII) and [3H]oxytocin ([3H]OT) were microperfused through rabbit kidney tubule segments in vitro. The reabsorption and tubular sequestration of radioactive label were determined, and the collection fluid was electrophoretically analyzed. The data suggest that [14C]AII is extensively hydrolyzed in the pars recta of the nephron and is rapidly reabsorbed across the tubular epithelium. Under similar experimental conditions, hydrolysis of [3H]OT was not observed in either the proximal straight or cortical collecting tubule segment, and the rate of reabsorption was low. Thus, tubular handling of OT appears to differ from that of AII, probably because of differences in molecular structure.
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PMID:Handling of angiotensin II and oxytocin by renal tubular segments perfused in vitro. 85 Nov 89

In attempting to design an antagonist of the antidiuretic response to arginine-vasopressin (AVP) [1-deaminopenicillamine,4-valine,8-D-arginine]vasopressin (dPVDAVP) was synthesized by the solid-phase method and assayed for antidiuretic, vasopressor, and oxytocic activities. dPVDAVP has an antidiuretic potency of 123 +/- 22 units/mg, one-tenth that of its parent [deamino,4-valine,8-D-arginine]vasopressin (dVDAVP). Like dVDAVP its antidiuretic effect in conscious diabetes insipidus rats is greatly prolonged when compared to AVP. dPVDAVP causes a prolonged inhibition of vasopressor responses to AVP but not to norepinephrine or angiotensin II. It has an antivasopressor pA2 value of 7.82 +/- 0.05 when tested against AVP. Thus the penicillamine substitution at position 1 in dVDAVP increased its antivasopressor activity sixfold (dVDAVP has a pA2 value of 7.03 +/- 0.11). dPVDAVP is thus the most potent vasopressor antagonist yet reported. dPVDAVP was also found to be a potent inhibitor of the in vitro oxytocic response to oxytocin (pA2 value = 7.23 +/- 0.04). dPVDAVP with its potent and specific ability to antagonize the vasopressor effects of AVP should be a useful pharmacological tool with which to explore the possible participation of AVP's potent vasoconstrictor properties in cardiovascular regulation in physiological and pathological states.
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PMID:[1-deaminopenicillamine,4-valine]-8-D-arginine-vasopressin, a highly potent inhibitor of the vasopressor response to arginine-vasopressin. 92 26


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