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)

We investigated the hypothesis that vasopressin, angiotensin II, and norepinephrine stimulate the synthesis of vasodilatory prostaglandins in cultured vascular smooth muscle cells from rat mesenteric arteries. The major prostaglandin synthesized by subcultured vascular smooth muscle cells was PGI2 (measured as its stable metabolite 6-keto-PGF1 alpha) followed by 1/20th to 1/40th as much PGF2 alpha and PGE2. Vasopressin and angiotensin II dose dependently increased prostaglandin synthesis with a half-maximal stimulatory concentration of the order of 1 X 10(-8) M for both peptides. However, vasopressin could provoke the synthesis of two to three times as much PGI2 as angiotensin II, at maximally effective concentrations. Vasopressin's ability to provoke prostaglandin synthesis depended on its pressor activity as demonstrated by the ability of a potent antipressor analogue of vasopressin, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine] arginine vasopressin, to completely inhibit vasopressin-provoked prostaglandin synthesis. Moreover, 1-desamino-8-D-arginine vasopressin, an analogue having full antidiuretic but no pressor activity was much less effective than vasopressin as a prostaglandin-stimulatory agent. Unlike peptide vasoconstrictors, norepinephrine (10(-9) to 10(-5) M) had no ability to stimulate prostaglandin synthesis in vascular smooth muscle cells. We conclude that the potent vasodilator PGI2, released from vascular smooth muscle cells, may buffer the peptide-induced vasoconstriction.
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PMID:Vasoconstrictor-evoked prostaglandin synthesis in cultured vascular smooth muscle. 661 60

15-cyclopentyl-omega-pentanor-5(E)-carbacyclin (ONO 41483), a chemically stable carboprostacyclin analogue, was 3.3 times less active than prostacyclin but was 2.6 times more active than carboprostacyclin in inhibiting aggregation of ADP-induced baboon platelet in vitro. On human platelets in vitro, ONO 41483 was 9.4 times less active than prostacyclin and 12.7 times more active than carboprostacyclin. ONO 41483 was 3.7 times less active than prostacyclin but was 2.2 times more active than carboprostacyclin in producing a fall in arterial blood pressure in anaesthetised baboons. Intravenous and oral administration of ONO 41483 in baboons produced ex vivo inhibition of ADP-induced platelet aggregation at doses that did not affect blood pressure or heart rate. In addition, bolus intravenous doses (3 to 10 micrograms/kg) of ONO 41483 reversed vasopressin-induced ECG changes in the monkey, suggesting an ability of the compound to relieve coronary spasm.
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PMID:Inhibition of platelet aggregation and reversal of vasopressin-induced ECG changes by a carboprostacyclin analogue, ONO 41483, in primates. 675 59

The vascular actions of several prostanoids and arachidonate lipoxygenase products were investigated on the gastric circulation of rat and rabbit in vitro perfused with Krebs' solution. Under resting conditions, prostacyclin and PGE2 produced small decreases in perfusion pressure with prostacyclin being the more potent. During vasoconstriction induced by infusion of noradrenaline, vasopressin or angiotensin II, prostacyclin was 20-40 times as active as PGE2 as a gastric vasodilator in rat or rabbit stomach. PGF2 alpha was a less potent vasoconstrictor than noradrenaline, while the epoxy-methano endoperoxide analogue produced a long-lasting vasoconstriction. The putative metabolite, 6-oxo-PGE1 was less active than prostacyclin as a vasodilator, having comparable activity to PGE1, whereas 6-oxo-PGF1 alpha had very little activity. The endoperoxide, PGH2 reduced perfusion pressure, this effect being inhibited by concurrent infusion of 15-HPETE. The vasodilation induced by arachidonic acid was likewise reduced by 15-HPETE, and abolished by indomethacin infusion. The arachidonate lipoxygenase hydroperoxides were vasodilator in the gastric circulation, the rank order of potency being 12-HPETE greater than 11-HPETE greater than 5-HPETE greater than 15-HPETE in both rat and rabbit stomach. It is possible that such vasoactive lipoxygenase products, may play modulator roles in the gastric mucosa.
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PMID:Investigation of the vascular actions of arachidonate lipoxygenase and cyclo-oxygenase products on the isolated perfused stomach of rat and rabbit. 679 98

Current knowledge on prostaglandin biosynthesis is reviewed, centering on how PGs participate in the regulation of vascular tone and the prevention of platelet deposition on endothelial surfaces. Discussion includes review of the vasoactivity of the PG endoperoxides, thromboxane, prostacyclin, and prostaglandin E2; prostaglandin-catabolizing enzymes; polyunsaturated fatty acid precursors; nutritional factors; antidiuretic hormone; and interrelations of PGs with the renin-angiotensin system.
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PMID:Prostaglandins, antidiuretic hormone and renin angiotensin system. 679 18

The present experiments were performed to investigate whether the responses of the myoepithelium to several drugs would be of a parallel nature with those of the vascular smooth muscle in the lactating mammary gland of goats. The drugs were injected into the mammary artery. Kallikrein, bradykinin, oxytocin, and acetylcholine caused marked milk-ejection with vasodilation in a dose-dependent manner. Marked milk-ejections with high doses of oxytocin were observed despite of accompanying vasoconstriction. The relative order of their potency in milk-ejection activity was kallikrein greater than bradykinin greater than oxytocin greater than acetylcholine: 1 greater than 1/100 greater than 3/1000 greater than 5/1000000. As for the vasodilator activity, the relative potency of the drugs was in the same order: 1 greater than 1/10 greater than 1/1000 greater than 1/10000. Catecholamines, histamine, serotonin, angiotensin-II, vasopressin and high doses of prostaglandin E2 caused dose-dependent vasoconstriction. Isoprenaline, pilocarpine, adenosine, PGI2 and low doses of PGE2 caused dose-dependent vasodilation. But these drugs did not affect milk-ejection. PGE1 decreased milk-ejection and was accompanied by vasodilation. From these experiments it is suggested that the relative order of the potency of secretagogues in milk-ejection activity and in vasodilator activity is nearly equal. It is also suggested that some drugs are different in their effects on the myoepithelium and on the vascular smooth muscle of the lactating mammary gland.
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PMID:Pharmacological effects of several drugs on the myoepithelium and the vascular smooth muscle of the lactating mammary gland in goats. 692 Feb 63

Using newly develop radioimmunoassay for 6-keto-prostaglandin F1 alpha and 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha, the plasma concentrations of these two prostacyclin derivatives were measured in anaesthetized cats. After the administration of angiotensin II, which releases prostacyclin into the circulation, concentrations of both derivatives rose simultaneously, the major immunoreactivity being 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha. Angiotensin II-induced prostacyclin release was not caused by vasoconstriction alone, since comparable vasopressor responses to noradrenaline and vasopressin were not accompanied by increases in prostacyclin plasma levels. Injection of exogenous prostacyclin resulted in a shortlasting peak of 6-keto-prostaglandin F 1 alpha, which rapidly declined (t 1/2: 1.29-1.52 min). 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha appeared with an t 1/2 of 0.48-1.38 min and was eliminated with a t 1/2 of 8.0-9.0 min. Due to its longer half-life in the circulation 6,15-diketo-13,14-dihydro-prostaglandin F 1 alpha again was the predominant derivative after 3 min. These data suggest that in vivo prostacyclin is mainly inactivated by the 15-hydroxy-PG-dehydrogenase-, delta 13-reductase-pathway, rather than by hydrolysis. Therefore, 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha seems to be a better indicator of prostacyclin plasma levels than 6-keto-prostaglandin F1 alpha, although under certain conditions the additional determinations of this product of hydrolysis can be valuable.
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PMID:Formation and elimination of prostacyclin metabolites in the cat in vivo as determined by radioimmunoassay of unextracted plasma. 703 51

Although prostacyclin (PGI2) causes an increase in resting gastric mucosal blood flow, this effect is not thought to be correlated with its cytoprotective action. This study questions that hypothesis by assessing whether PGI2 cytoprotection occurs in the presence of decreased gastric mucosal blood flow. Twenty-four miniature swine were anesthetized with chloralose, ventilated, and catheterized to measure cardiac output and arterial pressure and to inject microspheres. An orogastric tube was placed for infusion of 2.5% autogenous bile in isotonic HCl (2 ml/kg/hr). Four experimental groups were used: I, control (no drugs); II, vasopressin (0.25 U/min intravenously); III, PGI2 (0.1 micrograms/kg/min intravenously); and IV, vasopressin and PGI2 combined. Gastric mucosal blood flow was documented at baseline and at 1, 2, and 3 hours of drug infusion by radiolabeled-microsphere technique. Stomachs were harvested and photographed, and lesions were scored (0 to 3) by blinded observers. Gastric mucosal blood flow was decreased (50%) in both groups that received vasopressin, increased (300%) in animals that received PGI2 alone, and unchanged in controls. All animals that received vasopressin, whether alone or with PGI2, developed mucosal injury (mean score 2.5 versus (2.2). Group I and group III animals did not develop lesions. The results of this study demonstrate that PGI2 failed to elevate gastric mucosal blood flow, which was already depressed to vasopressin, and that PGI2 failed to protect the gastric mucosa from injury in the presence of reduced blood flow. This suggests that PGI2 cytoprotection is linked to its effect on gastric mucosal blood flow.
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PMID:Prostacyclin-mediated gastric cytoprotection is dependent on mucosal blood flow. 704 95

Responses to angiotensin II, bradykinin and arginine vasopressin were compared in helical strips of canine pulmonary arteries and veins. Angiotensin II contracted the artery but relaxed the vein strip. The artery contraction was augmented by indomethacin and aspirin and was abolished by losartan. The vein relaxation was not affected by endothelium denudation but was abolished by the cyclooxygenase inhibitors, a prostaglandin I2 synthase inhibitor and losartan. The bradykinin-induced artery relaxation was inhibited by endothelium denudation, NG-nitro-L-arginine (L-NA) or indomethacin and abolished by their combined treatment. The vein relaxation produced by bradykinin was endothelium-independent and was abolished by indomethacin. Vasopressin produced a slight relaxation in the arteries, which was abolished by endothelium denudation and L-NA. The vein relaxation produced by vasopressin was abolished by endothelium denudation and combined treatment with L-NA and indomethacin. It may be concluded that (1) activation of angiotensin AT1 receptor subtype in smooth muscle produces contraction and also relaxation due to prostaglandin I2 release; the former predominates over the latter in the artery, whereas only the latter is operative in the vein, (2) the bradykinin-induced relaxation is due to nitric oxide (NO) from the endothelium and prostaglandin I2 from subendothelial tissues in the artery and solely to prostaglandin I2 in the veins, and (3) the vasopressin-induced relaxation is mediated by endothelial NO in the artery, and NO and prostaglandin I2 in the vein.
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PMID:Comparison of responses of canine pulmonary artery and vein to angiotensin II, bradykinin and vasopressin. 749 82

Prostaglandin E2 (PGE2) inhibits vasopressin-stimulated water conductivity (AVP-Lp) and inhibits Na+ reabsorption in the rabbit cortical collecting duct (CCD). Inhibition of Na+ reabsorption is mediated by increased intracellular calcium ion concentration ([Ca2+]i). Prostacyclin (PGI2) has also been shown to inhibit Na+ reabsorption in the CCD. The present studies were designed to examine the effect of the PGI2 agonist, Iloprost (ILP), on AVP-Lp and [Ca2+ in the isolated perfused rabbit CCD and to determine whether ILP activates different receptors than PGE2. ILP and PGE2 each maximally inhibited AVP-Lp equipotently at 10(-7) M. When CCDs were exposed to PGE2 and ILP simultaneously, or if PGE2 was added in the presence of ILP, inhibition of AVP-Lp was additive. Additivity was not observed if the PGI2 agonist, carbaprostacyclin (c-PGI2), was added with ILP, or if the PGE2 agonist, sulprostone, was added with PGE2, or if ILP was added to CCDs preexposed to PGE2. In fura 2-loaded CCD, ILP and PGE2 added separately increased [Ca2+]i. The response to c-PGI2 could be desensitized by prior exposure to ILP. ILP did not cause desensitization to PGE2, but PGE2 could desensitize the CCD to ILP. We conclude that PGI2 inhibits AVP-Lp by activation of a novel IP3 prostacyclin receptor and increases [Ca2+]i by activation of an IP1 prostacyclin receptor in the rabbit CCD. Functional evidence is presented that PGI2 cannot occupy PGE2 receptors and that PGE2 can occupy but cannot activate PGI2 receptors linked to inhibition of AVP-Lp.
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PMID:Rabbit cortical collecting ducts express a novel prostacyclin receptor. 753 Sep 13

While many observations indicate that prostaglandins may act as positive regulators of hepatocyte proliferation, the underlying mechanisms are not known. We have examined some of the signal pathways in the growth response induced by prostaglandins in hepatocytes, with particular focus on adenylyl cyclase and phosphoinositide-specific phospholipase C. Adult rat hepatocytes were cultured as primary monolayers in serum-free medium in the presence of EGF and insulin. PGE2 or PGF2 alpha (added 0-3 h after plating) enhanced the incorporation of [3H]-thymidine into DNA (measured at 50 h); at 100 microM the stimulation was about threefold PGI2 and PGD2 also showed significant but smaller stimulatory effects. No significant increase in the level of cyclic AMP (cAMP) was detected in response to any of the prostaglandins. Low concentrations of glucagon (0.1-10 nM), a potent activator of hepatic adenylyl cyclase, or 8-bromo-cAMP (0.1-10 microM) enhanced the DNA synthesis. When 8-bromo-cAMP was used in maximally effective concentrations, no further stimulation was obtained by combining it with glucagon, whereas the effects of PGE2 and 8-bromo-cAMP were completely additive. All the prostaglandins also showed additivity with the effect of glucagon on the DNA synthesis. PGE2, PGF2 alpha, PGI2, and PGD2 increased intracellular inositol-1,4,5-trisphosphate (InsP3), with a relative order of efficacy roughly corresponding to their activity as stimulators of DNA synthesis. Increases in cytosolic free Ca2+, as measured in single cells, were elicited in a majority of the hepatocytes by all these prostaglandins at 1 microM. Supramaximal concentrations of vasopressin, a strong activator of phospholipase C in hepatocytes, acted additively with PGE2 on the DNA synthesis. Pretreatment of the hepatocytes with a concentration of pertussis toxin that prevented the inhibitory effect of PGE2 on glucagon-induced cAMP accumulation did not abolish the ability of PGE2 to stimulate the DNA synthesis. The results do not support a role for adenylyl cyclase activation in the stimulatory effect of prostaglandins on hepatocyte growth. While the data are compatible with an involvement of phosphoinositide-specific phospholipase C in the growth-promoting effect of prostaglandins in cultured rat hepatocytes, they suggest this may not be the sole mechanism.
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PMID:On the mechanisms of the growth-promoting effect of prostaglandins in hepatocytes: the relationship between stimulation of DNA synthesis and signaling mediated by adenylyl cyclase and phosphoinositide-specific phospholipase C. 765 56


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