Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intragastric administration of lysine vasopressin (LVP) to rats is used as a model to study the biological activity of orally administered peptide hormones. Using a modification of the antidiuretic assay of Sawyer, LVP given by stomach tube caused a significant antidiuresis that was dose dependent in doses of 300 to 2000 mU. The simultaneous administration of the protease inhibitor, Trasylol, increased the antidiuretic effect of LVP. The synthetic peptide (1-deamino, 4 valine)-8-D-arginine-vasopressin also caused a dose-dependent prolonged and significant antidiuresis. No pressor effect was observed after intragastric administration of LVP in doses up to 40 U/rat. We are now using this model to test other procedures for enhancing the activity of lysine vasopressin administered in the gastrointestinal tract such as encapsulation into liposomes. The information gained with vasopressin will then be applied to insulin with the ultimate goal of making oral administration practical.
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PMID:A model for the study of the oral administration of peptide hormones. 31 22

Proteolytic enzyme inhibitors were examined as absorption enhancers for the nasal delivery of vasopressin (AVP) and desmopressin (1-d-8-DAVP) in rats. Aprotinin, soybean trypsin inhibitor, and camostat mesilate were used as enzyme inhibitors. The nasal absorption of AVP and 1-d-8-DAVP was evaluated by measuring its antidiuretic effect. Nasal administration of AVP (0.005 IU/kg) or 1-d-8-DAVP alone (2.5 ng/kg) produced a small antidiuretic effect. Coadministration with aprotinin (1000 and 10000 KIU/kg) or soybean trypsin inhibitor (1.25 and 6.25 mM) did not change the antidiuretic effect. However, coadministration with camostat mesilate (1 to 50 mM) significantly increased the antidiuretic effect and, thus, the nasal absorption of AVP and 1-d-8-DAVP. The activities of aminopeptidase, cathepsin-B, and trypsin in the nasal mucosal tissue of rats were 7 nmol/min/mg protein, 0.7 nmol/min/mg protein, and 4.6 pmol/min/mg protein, respectively. Aprotinin and soybean trypsin inhibitor inhibited only the trypsin activity, whereas camostat mesilate inhibited aminopeptidase and trypsin activities. Aprotinin (MW 6500) and soybean trypsin inhibitor (MW 8000), with relatively high molecular weights, may not permeate into the nasal mucosal tissue. In contrast, camostat mesilate is slowly absorbed (8%/hr) and could inhibit the proteolytic activity in the nasal mucosa, resulting in enhanced nasal absorption of AVP and 1-d-8-DAVP.
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PMID:Effects of proteolytic enzyme inhibitors on the nasal absorption of vasopressin and an analogue. 172 82

We contrasted the renal effects of vasopressin in Brattleboro rats with and without pretreatment with aprotinin (20,000 KIU kg-1). In both treatment groups, vasopressin injected at 3 mU kg-1 sec caused in conscious rats elevation of urine osmolality and reduction of urine flow and urinary excretion of total solutes. However, these effects of vasopressin were significantly greater in aprotinin pretreated rats than in rats without aprotinin treatment. In ketamine-pentobarbital-anesthetized rats without aprotinin pretreatment, vasopressin infused at 2 mU kg-1 hr-1 elevated urinary kinin excretion but did not affect urine flow rate or osmolality; in contrast, in aprotinin-pretreated rats, the same dose of vasopressin did not increase urinary kinins but caused elevation of urinary osmolality and reduction of urine flow, solute excretion, and glomerular filtration rate. Aprotinin pretreatment in anesthetized rats also blunted the rise in kinin excretion elicited by vasopressin at a higher dosage, 5 mU kg-1 hr-1, but did not potentiate the vasopressin-induced antidiuresis. We conclude that aprotinin facilitates the expression of the antidiuretic effect of vasopressin at a low, but not at a high dosage. This effect of aprotinin may be a consequence of: renal kallikrein inhibition which prevents augmentation of renal kinins in response to increased vasopressin levels, or other unrecognized properties of aprotinin.
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PMID:Augmentation by aprotinin of the renal response to vasopressin. 243 37

Vasoactive peptides contain a high proportion of proline residues which make them resistant to hydrolysis by many peptidases. However, post proline cleaving enzyme (PPCE; EC 3.4.21.26), a proline specific endopeptidase which specifically hydrolyzes internal peptide bonds on the carboxyl side of proline residues, has been shown to inactivate numerous vasoactive peptides including angiotensins, kinins, substance P, vasopressin and oxytocin. In order to determine whether PPCE could be involved in vascular metabolism of vasoactive peptides, we carried out localization and characterization studies of PPCE-like activity in hog aorta and mesenteric artery. PPCE was assayed fluorometrically at pH 7.0 using the specific PPCE substrate CBZ-Gly-Pro-4-methyl-coumarinylamide. The subcellular distribution of vascular PPCE was essentially the same as that of the cytosolic marker enzyme lactic dehydrogenase (LDH). PPCE was enriched six-fold in the cytosolic fraction (11.4 +/- 2.7 units/mg) and unlike the plasma membrane-bound proline specific exopeptidase dipeptidyl-(amino)peptidase IV (DAP IV; EC 3.4.14.5), little or no activity could be detected in the microsomal or plasma membrane fractions. Similar to PPCE characterized from other sites, vascular PPCE was stabilized and activated by dithiothreitol and EDTA, and inhibited by DFP, p-chloromercuriphenyl sulfonic acid, L-1-tosylamido-2-phenylethylchloromethyl ketone, Cu++, Ca++, and Zn++. Vascular PPCE was unaffected by inhibitors of trypsin and kallikrein (Aprotinin, ABTI), aminopeptidase M (bestatin, amastatin), neutral endopeptidase (phosphoramidon), angiotensin I converting enzyme (captopril) or carboxypeptidase N (MERGETPA). These data demonstrate that PPCE is present in vascular endothelium and/or smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular, post proline cleaving enzyme: metabolism of vasoactive peptides. 354 18

A dog model was established to measure the hemodynamic changes occurring during experimental pancreatitis. The effect of treatment with Trasylol and vasopressin, beginning 60 minutes after induction of pancreatitis was assessed by their effect on the pancreatic hemodynamics. The pancreatic arterial blood flow fell by 72 per cent in the dogs with induced pancreatitis and treated only with saline solution. In contrast, the pancreatic blood flow fell by 58 per cent in the Trasylol group and 80 per cent in the vasopressin group. In addition, vasopressin had a detrimental effect on the cardiac output. Neither treatment altered the changes noted in the systemic blood pressure. Trasylol had a slight beneficial effect on experimental pancreatitis when assessed by its effect on the pancreatic hemodynamics. In contrast, vasopressin had a detrimental effect on the pancreatic hemodynamics.
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PMID:The effect of Trasylol and vasopressin on experimental pancreatitis. 615 20

Aprotinin, a reversible inhibitor, and D-Phe-Phe-Arg-chloromethyl ketone (DPPA), an irreversible inhibitor of mammalian glandular kallikreins, decreased short-circuit current (SCC) in the isolated toad urinary bladder. Both were more potent and rapidly acting on the mucosal than serosal surface. The maximal inhibition in basal SCC was 29% for aprotinin and 41% for DPPA at concentrations of 7.0 X 10(-6) and 1.0 X 10(-5) M, respectively. SCC inhibition with mucosal aprotinin was reversed by rinsing, whereas inhibition with mucosal DPPA was not reversible. The presence of either agent in the mucosal bath inhibited the SCC increase to serosal vasopressin, but neither modified this response when present in the serosal bath. Neither agent affected basal or vasopressin-stimulated osmotic water permeability. Aprotinin did not prevent aldosterone-induced increases in SCC. Soybean trypsin inhibitor, an inhibitor of plasma but not glandular kallikrein, did not affect SCC. We postulate that these inhibitors of mammalian glandular kallikreins act upon some accessible serine proteinase(s) to reduce short-circuit current. This protein(s) might be an amphibian homologue of mammalian renal kallikrein.
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PMID:Inhibition of short-circuit current in toad urinary bladder by inhibitors of glandular kallikrein. 615 95

Carboxamidopeptidase, an enzyme which inactivates neurohypophyseal hormones, has been purified 3800-fold in an overall yield of 22% from toad skin, a neurohypophyseal hormone target organ, by (NH4)2SO4 fractionation, DEAE-Sephadex chromatography, and affinity chromatography on immobilized p-aminobenzamidine and concanavalin A-agrose. The purified enzyme is capable of inactivating both [8-arginine]vasopressin (AVP) and oxytocin by hydrolyzing the Arg8-Gly9-NH2 and the Leu8-Gly9-NH2 bonds, respectively, and can hydrolyze the ester substrates, benzoyl-L-arginine ethyl ester (BzArgOEt) and acetyl-L-trypsine ethyl ester, suggesting that the enzyme has both trypsin-like and chymotrypsin-like activities. Carboxamidopeptidase is maximally active at pH 7.5-8.5 for AVP and BzArgOEt and pH 7.0 for oxytocin. Carboxamidopeptidase is inhibited by ovoinhibitor, ovomucoid, Trasylol. lima bean trypsin inhibitor, concanavalin A, antipain, leupeptin, chymostatin, elastatinal, p-nitrophenyl p-guanidinobenzoate, and 4-methylumbelliferyl p-guanidinobenzoate but not by soybean trypsin inhibitor, alpha 1-antitrypsin, hirudin, pepstatin, bestatin, phosphoramidon, or cysteine. The enzyme is also inhibited by the serine protease inhibitor, diisopropyl phosphofluoridate (i-Pr2PF), and by the chloromethyl ketone derivatives of tosyllysine, tosylphenylalanine, and (benzyloxycarbonyl)phenylalanine, as well as by the sulfhydryl group reagent, p-(chloromercuri)benzoate (PCMB). Inhibition by PCMB is reversed by cysteine. The molecular weight determined by gel filtration in the presence of 1 MNaCl is approximately 100 000. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that the enzyme is composed of two identical subunits of 48 000 daltons. Each subunit consists of a heavy chain (28 000 daltons) and a light chain (19 000 daltons) joined by a disulfide bond(s). Labeling experiments using [3H]-i-Pr2PF showed that the enzyme active site is located in the heavy chain.
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PMID:Carboxamidopeptidase: purification and characterization of a neurohypophyseal hormone inactivating peptidase from toad skin. 676 14

Although many proteins and peptides were produced by gene-technology, their administration routes are limited to be i.v. route. To increase the clinical use of these products, oral dosage form is required. However, in the case of oral administration, proteins are degraded by digestive fluid having strong protease activity. To decrease the protease activity, protease inhibitors are administered concomitantly with proteins. Aprotinin, soybean trypsin inhibitors and gel-forming polymer such as Polycarbophil are representative protease inhibitors. Gel-forming polymers have both protease inhibiting activity and absorption enhancing effect on protein/peptides. The usefulness of these protease inhibitors have been suggested as an additive for the oral delivery of G-CSF and vasopressin derivatives.
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PMID:[Improvement of drug bioavailability using protease inhibitors]. 954 42

Pharmacological approaches to reduce blood transfusion include the protease inhibitor aprotinin, lysine-analogue antifibrinolytics synthetic arginine-vasopressin derivatives (DDAVP) and recombinant factor VII (rfVIIa). These agents are known to prevent the need for blood after major surgery (cardiac, hepatic, and orthopaedic). Among the nonhemostatic agents erythropoietin (EPO) may be effective to reduce blood requirements in medical and surgical patients. Aprotinin is consistently effective in reducing blood transfusion in cardiac and hepatic surgical procedures, but there is little data to support its use in elective orthopaedic surgery. Antifibrinolytics show no evidence of efficacy in cardiac and hepatic surgery and its use is not warranted in orthopaedic surgery. Limited data suggest that DDAVP may be effective when a defect in platelet function is demonstrated. rFVIIa emerges as a promising haemostatic agent with proven benefit to reduce bleeding in haemophiliacs with inhibitors but might also be effective in patients with thrombocytopenia and thrombopathy, as well as in life-threatening hemorrhage in postsurgical patients. Ongoing studies will established its role a possible "universal haemostatic agent". Hematopoietic cytokines, such as EPO, may have a place to avoid blood transfusion in a variety of clinical conditions, including cancer and critically ill patients.
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PMID:[Pharmacological alternatives to blood transfusion: what is new about?]. 1571 48