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 gastric incisions of rabbits intra-arterially infused with vasopressin were analyzed for collagen synthesis, tensile strength and inflammatory reaction for five, ten and 20 days from the time of wounding. Significant differences were looked for in the collagen content of treated and untreated wounds. Tensile strength of a strip of gastric wound with sutures removed was tested on a motor driven tensiometer. The breaking point of the strip in grams of weight required was used as the end point. A portion of tissue from the wound site of each of the 36 rabbits was processed for microscopic examination, and the resulting slides were labeled with code numbers to preserve blind conditions. The effect of vasopressin on the healing of a standard gastric incision in the rabbit was studied. When compared with those rabbits in the control study which were infused with a saline solution alone, no significant difference was found in tensile strength, inflammatory response or synthesis of new collagen, as determined by the hydroxyproline ratio. There would appear to be no adverse effects upon gastric wound healing as a result of intra-arterially infused vasopressin in the concentrations used in this experiment.
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PMID:The effect of vasopressin on gastric wound healing. 724 48

Effects of OP 1206 were studied on the cardiovascular system and platelet functions to assess OP 1206 as an antianginal agent. OP 1206 given orally at more than 100 micrograms/kg relieved vasopressin-induced ST depression of rat electrocardiogram (ECG), an animal model of angina pectoris, concomitant with slight hypotension. Intra-coronary injection of OP 1206 (1-100 ng/kg) in dogs resulted in a remarkable increase of coronary blood flow without any influence on heart rate, blood pressure, myocardial oxygen consumption and redox potential. Resistance in both large and small vessels of dog coronary artery was decreased by intravenous injection of OP 1206 (1-3 micrograms/kg). Platelet aggregation, adhesiveness, bleeding time, and thrombocytopenia induced by ADP and collagen infusion in guinea-pigs were inhibited by oral administration of OP 1206 at the same doses or doses less than those relieving vasopressin-induced ST depression of ECG. These results suggest that OP 1206 contributes to the improvement of cardiac imbalance between oxygen demand and supply, and suppression of thrombus formation in atherosclerotic heart.
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PMID:Pharmacological evaluation of OP 1206, a prostaglandin E1 derivative, as an antianginal agent. 744 63

Upon activation platelets show elevated protein tyrosine phosphorylation, and translocation of the protein tyrosine kinase pp60c-src from the plasma membrane to the cytoskeleton occurs. We therefore investigated whether tyrosine phosphorylation also increases in the cytoskeletal compartment. Here we show that almost identical patterns of phosphotyrosine-containing proteins are detectable in the cytoskeleton after platelet stimulation with compounds that directly (phorbol 12-myristate, 13-acetate) or indirectly (thrombin, vasopressin, collagen, ADP) activate protein kinase C. The apparent molecular masses of the proteins phosphorylated at tyrosine residues are 145, 130, 100, 85, 80, 60, 56, 54 and 38 kDa. Elevation of cyclic AMP by prostaglandin E1 had no effect. Concentrations of thrombin as low as 0.01 units per ml are able to cause tyrosine phosphorylation of multiple proteins. The time course of protein tyrosine phosphorylation for thrombin- and vasopressin-stimulated platelets revealed a rapid increase in the cytoskeleton within 5 to 20 s following activation consistent with a role in early events of platelet function.
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PMID:Rapid protein tyrosine phosphorylation in the cytoskeleton of stimulated human platelets. 753 10

The functional consequence of cyclic AMP-dependent phosphorylation of rap1B for stimulus-induced platelet activation is not known. Platelets were pretreated with the stable prostacyclin-analogue iloprost and resuspended in plasma without iloprost. Western blot analysis showed that rap1B was completely converted into its phosphorylated form in the iloprost-pretreated platelets. Surprisingly, the platelets that contained phosphorylated rap1B were found to respond fully to activation by a wide variety of stimuli: aggregation upon stimulation by collagen, phorbol ester, vasopressin, ADP, epinephrine, and ATP-secretion from dense granules induced by collagen, thrombin-receptor activating peptide, vasopressin and phorbol ester were unchanged as compared to control. The results indicate that cyclic AMP-dependent phosphorylation of rap1B does not play a role in the inhibition of the various signal transduction pathways that lead to platelet aggregation and dense granule secretion.
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PMID:Phosphorylation of rap1B by protein kinase A is not involved in platelet inhibition by cyclic AMP. 768

Thrombin binds at least to two sites of the platelet surface; to the recently cloned thrombin receptor [Vu, T. K., Hung, D. T., Wheaton, V. I. & Coughlin, S. R. (1991) Cell 64, 1057-1068] and to glycoprotein Ib. In the present study, the decrease of pertussis-toxin-dependent ADP-ribosylation of membrane and soluble inhibitory guanine-nucleotide-binding alpha (Gi alpha) proteins was measured after platelet stimulation with a thrombin-receptor-activating peptide (TRAP), and compared to stimulation with thrombin. Stimulation of intact platelets with TRAP decreased the pertussis-toxin-dependent ADP-ribosylation of the major membrane 41-kDa Gi alpha protein and the minor soluble 40 kDa Gi alpha protein recently described in platelets [Gennity, J. M. & Siess, W. (1991) Biochem. J. 279, 643-650]. The kinetics and extent of the decrease of pertussis-toxin-dependent ADP-ribosylation after stimulation of TRAP were similar to the effect of thrombin. The decrease of pertussis-toxin-dependent ADP-ribosylation of the soluble Gi alpha protein was more pronounced and observed at lower agonist concentrations than the decrease of the membrane Gi alpha protein. Desensitization of the thrombin receptor by incubating platelets with a low concentration of TRAP reduced the subsequent decrease of pertussis-toxin-dependent ADP-ribosylation of Gi alpha proteins, evoked by TRAP or thrombin. Platelet stimulation with gamma-thrombin that does not bind to glycoprotein Ib also showed a decrease in the pertussis-toxin-dependent ADP-ribosylation of the soluble and membrane Gi alpha proteins. Treatment of platelets with the stable prostacyclin analog, iloprost, reduced the decrease of pertussis-toxin-dependent ADP-ribosylation of Gi alpha proteins induced by TRAP or thrombin. Among other platelet stimuli tested (endoperoxide/thromboxane analog U44619, collagen, ADP, vasopressin), only U44619 decreased the pertussis-toxin-dependent ADP-ribosylation of the soluble and membrane Gi alpha proteins to a degree comparable to TRAP. It is concluded that the thrombin-induced activation of both the membrane and soluble Gi alpha proteins in platelets occurs via stimulation of the recently cloned thrombin receptor and is independent of the binding of thrombin to glycoprotein Ib. Furthermore, the coupling thrombin receptor/Gi protein is reduced by intracellular cAMP.
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PMID:Activation of the cloned platelet thrombin receptor decreases the pertussis-toxin-dependent ADP-ribosylation of the membrane and soluble inhibitory guanine-nucleotide-binding-alpha proteins. Inhibition by the prostacyclin analog, iloprost. 768 67

Administration of 1-desamino-8-D-arginine vasopressin (DDAVP), a synthetic vasopressin derivative, causes an increase in plasma factor VIII and von Willebrand factor (vWF). Recently, evidence has become available that intravenous infusion of DDAVP shortens the prolonged bleeding times in some patients with primary platelet defects even though their plasma levels of vWF and FVIII are normal prior to drug administration. The mechanism of this effect of DDAVP has not been well defined and it has been generally considered that the beneficial effect on the bleeding time is related to the rise in plasma vWF and its impact on platelet adhesion to subendothelial components including collagen, an important step in hemostasis. Thus, studies aimed at understanding the effect of DDAVP have focused on vWF-mediated adhesion of platelets to the subendothelium. For example, Sakariassen et al studied the platelet adherence to human arterial subendothelium and concluded that DDAVP improves hemostasis by causing enhanced vWF-mediated platelet adherence. This mechanism would explain the shortening of the bleeding time in patients with milder forms of vWD with subnormal levels of vWF. But patients with congenital platelets defects have normal plasma vWF raising the possibility that there may be other mechanisms contributing to the beneficial effect of DDAVP. It is clear that platelets can interact directly with collagen, mediated by specific platelet binding sites. Further, DDAVP binds to platelets even though by itself does not activate them. The present investigation was designed to elucidate whether DDAVP had any effect on the direct adhesion of platelets to collagen in the absence of mediation by vWF. Hashemi et al have suggested that the effect of DDAVP on endothelial cell release of vWF is mediated by an as yet uncharacterized intermediate factor(s) released from peripheral mononuclear cells. Therefore, we studied the effect also of plasma samples obtained from patients treated with DDAVP on adhesion of platelets to collagen.
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PMID:Lack of effect of 1-desamino-8-D-arginine vasopressin on direct adhesion of platelets to collagen. 769 Sep 94

Human blood platelets contain high levels of non-receptor protein tyrosine kinases of the Src family, particularly pp60c-src, suggesting an important role for these enzymes in platelet physiology. Indeed, in response to various agonists of platelet function, a number of proteins become phosphorylated at tyrosine residues. However, no enzymic activation of an Src-related tyrosine kinase has yet been shown in platelets. In searching for the kinase(s) responsible, we found that all agonists tested that directly or indirectly activate protein kinase C in platelets (phorbol 12-myristate, 13-acetate, thrombin, vasopressin, collagen, calcium ionophore A23187) increased the overall activity of pp60c-src determined by IgG phosphorylation in an immunocomplex assay in the presence of low ATP concentrations. On the other hand, elevation of cyclic AMP directly by forskolin or indirectly by prostaglandin E1, or elevation of cyclic GMP by sodium nitroprusside did not significantly affect the activity of the enzyme. To substantiate the differences in enzyme activity, we determined Km and Vmax, values of pp60c-src from resting and thrombin-stimulated platelets. Thrombin treatment increased substrate affinity of pp60c-src as indicated by a 2- to 3-fold decrease in the Km values for ATP and the exogenous protein substrate casein. Vmax. values were only slightly altered under the assay conditions used. To further rule out modifications of pp60c-src in phosphorylation as a probable cause of the changed substrate affinity, we analysed tryptic phosphopeptides of immunoprecipitated, 32P-labelled pp60c-src of unstimulated and stimulated platelets. The platelet agonists listed above induced an increase in pp60c-src phosphorylation at Ser-12, which is the amino acid phosphorylated by protein kinase C. Surprisingly, we found that elevation of cyclic AMP did not affect 32P labelling of pp60c-src. On the basis of our data, we suggest that phosphorylation at Ser-12 might be one of the signal-triggering events that cause the increase in substrate affinity of pp60c-src.
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PMID:Substrate affinity of the protein tyrosine kinase pp60c-src is increased on thrombin stimulation of human platelets. 769 43

We experienced three patients who have collagen diseases with respiratory failure accompanied by hyponatremia. They were one systemic lupus erythematosus patient with interstitial pneumonia, one rheumatoid arthritis patient with acute pneumonitis, and one dermatomyositis patient with pulmonary fibrosis and organizing pneumonia. In all 3 patients, hyponatremia appeared along with a decrease in arterial O2 partial pressure (PaO2) and the hyponatremia tended to improve when the PaO2 increased after inhalation of oxygen, even though their respiratory failure were not improved. In dermatomyositis patient, serum Na levels were over-corrected after increase in PaO2. The serum and urine osmolality, serum antidiuretic hormone (ADH) levels and clinical pictures demonstrated a presence of inappropriate secretion of ADH (SIADH) in all 3 cases when hyponatremia and hypoxia appeared. A close association between hyponatremia and hypoxia observed in 3 patients strongly suggested that their SIADH were associated with hypoxia since SIADH could be demonstrated by hypoxia. Therefore, it is important to realize that hypoxia-induced hyponatremia will be promptly corrected to hypernatremia by an oxygen inhalation, which could cause a lethal central pontine myelinolysis.
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PMID:[Three cases of respiratory failure of collagen diseases accompanied by syndrome of inappropriate secretion of antidiuretic hormone (SIADH)]. 780 Dec 3

It has long been known that a number of diseases affecting the kidney are the result of genetic defects passed on through the generations. Whereas some of these defects are rare, others, eg, the cystic diseases, are among the most common. Our understanding of the underlying pathobiology in these disorders based on physiologic and cell biologic studies is variable--we suspect that the V2 vasopressin receptor is defective in nephrogenic diabetes insipidus; we know that the glomerular basement membrane in Alport syndrome is abnormal; we suspect that a tumor suppressor gene is defective in Wilms tumor; and we lack a unifying hypothesis regarding cystic degeneration of the kidney. The advent and rapid progress of molecular biology have permitted an entirely new approach to understanding these diseases, allowing the expected identification of mutations in the V2 receptor, the unexpected finding that a novel collagen gene is responsible for many Alport syndrome cases, and the somewhat less-unexpected finding that only one of several genes responsible for renal cancers has been identified. Further, we are beginning to unravel the complex pathways responsible for cystic changes in the kidney. This review integrates these molecular biologic discoveries with the known pathobiology of disease to achieve a more complete understanding of the whole process.
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PMID:Inherited diseases of the kidney. 792 3

Platelets respond through discrete receptors to a number of physiological agonists and foreign surfaces with a sequence of measurable responses: shape change, aggregation, secretion and arachidonate liberation. Three secretory responses are distinguished: exocytosis of substances from (1) dense granules, (2) alpha-granules and (3) lysosomes. Free arachidonate, liberated from phospholipids by phospholipase A2, is rapidly converted (by oxygenation) to prostaglandins and thromboxanes which, together with secreted ADP and close cell contact, will cause further platelet activation through 'positive feedback' (autocrine stimulation). Some agonists are classified as 'weak' (ADP, vasopressin, platelet-activating factor [PAF], serotonin) because they depend on autocrine stimulation to promote the full sequence of responses, while others are 'strong' agonists (thrombin, collagen) and activate all responses directly without autocrine stimulation. Adrenaline, long thought to be a platelet agonist per se, most probably acts by amplifying the activation brought about by other, proper, agonists. Such synergistic interaction among agonists is very typical for platelet activation and most likely takes place in vivo. Shape change, aggregation and secretion(s) may be tested by flow cytometry or electron microscopy in vitro under conditions that probably reflect the in vivo situation. However, the aggregation response to weak agonists in vitro is dependent on the extracellular [Ca2+], with biphasic aggregation at the low [Ca2+] present when citrate is used as anticoagulant (or in suspension of washed platelets) but not at the physiological [Ca2+] present in platelet-rich plasma from heparinized blood.
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PMID:Significance of testing platelet functions in vitro. 801 28


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