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)

TPA (12-O-tetradecanoylphorbol-13-acetate) is an effective tumor promoter that affects a variety of ion transport processes. To examine the relationship between effects on transport and growth and differentiation, we have been studying the actions of TPA on frog skin, a particularly well-characterized epithelium. We have reported that high concentrations of TPA stimulate base-line short-circuit current (ISC) and inhibit the subsequent natriferic action of vasopressin. The current study of 89 preparations extends those findings. The Km of the stimulatory effect of TPA is approximately 3 nM; this high affinity indicates that the transport phenomenon does not simply reflect a nonspecific interaction of phorbol ester with the plasma membranes. TPA acts largely or entirely at the mucosal surface of both split and whole skins; thus the sidedness of the effect does not arise from adsorption onto the underlying connective tissue when TPA is applied to the serosal surface of whole skin. Amiloride, an inhibitor of apical Na+ entry, abolishes ISC across frog skins pretreated with TPA. The phorbol ester also increases ISC across split skins, preparations which do not produce net Cl-transport. Indomethacin (1 microM) blocks PGE1 release, but does not alter the response to TPA at a fivefold lower concentration than previously used. NDGA (nordihydroguaretic acid, 10 microM), an inhibitor of the lipoxygenase pathway, partially inhibited the responses of ISC to 8 nM TPA. The present results indicate that frog skin is highly responsive to TPA at concentrations known to activate protein kinase C in broken-cell preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of TPA on short-circuit current across frog skin. 310 64

1. The role of endothelium-derived relaxing factor (EDRF) in the action of vasodilator (acetylcholine, histamine, nitroprusside) and vasoconstrictor (noradrenaline, vasopressin) drugs on vascular resistance in the isolated perfused kidney and mesentery of the rat was studied. 2. Acetylcholine (EC50 = 0.18 +/- 0.05 nmol and 3.1 +/- 0.06 nmol, n = 8) and histamine (EC50 = 31.2 +/- 4.9 nmol and 46.2 +/- 3.9 nmol, n = 8) produced dose-related vasodilatation in noradrenaline-preconstricted (i.e. 'high tone') rat renal and mesenteric blood vessels. The response to both vasodilators (but not nitroprusside) was abolished by infusion of CHAPS (4.7 mg ml-1, 30 s). By use of an immunocytochemical staining procedure CHAPS was demonstrated to remove vascular endothelial cells lining intrarenal blood vessels. 3. Gossypol (3 microM), metyrapone (10 microM) and nordihydroguaiaretic acid, (NDGA, 30 microM), presumed inhibitors of EDRF biosynthesis, reduced or abolished the response to acetylcholine and histamine in perfused kidney and mesentery of the rat without affecting vasodilatation due to nitroprusside. Mepacrine (10 microM) similarly abolished the response to acetylcholine and histamine but in addition, reduced the response to nitroprusside in both preparations. 4. Methylene blue (100 microM), a presumed antagonist of the effect of EDRF, abolished vasodilatation due to acetylcholine and histamine and reduced the response to nitroprusside in perfused rat kidney and mesentery. Superoxide dismutase, SOD (15 u ml-1), was without effect. 5. While CHAPS treatment significantly augmented the vasoconstrictor response to both noradrenaline and vasopressin in perfused renal and mesenteric vessels this effect was not mimicked by metyrapone or gossypol suggesting that the enhanced effect of vasopressor agents in CHAPSperfused rat organs is due to the removal of a permeability barrier rather than impaired EDRF formation. 6. Responses to vasoconstrictor and vasodilator drugs in the perfused kidney and mesentery were obtained in the presence of indomethacin (8 microM) which produced in excess of 90% inhibition of prostacyclin (PGI2) release as measured by radioimmunoassay of 6-oxo-prostaglandin F1 alpha,. (6-oxo- PGF1 alpha) in the Krebs effluent. 7. We provide evidence that EDRF mediates the vasodilator response to acetylcholine and histamine in resistance blood vessels in perfused rat kidney and mesentery. The possibility that EDRF has a physiological role to play in regulating the calibre of resistance blood vessels is discussed.
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PMID:Endothelium-derived relaxing factor and the effects of acetylcholine and histamine on resistance blood vessels. 326 34

This study was performed to examine an involvement of adenohypophysial arachidonic acid metabolites in the local mechanisms controlling the release of peptide hormones from the corticotrope cells of the anterior pituitary gland. Therefore, we investigated the effect of blockers of the lipoxygenase (nordihydroguaiaretic acid, NDGA), cyclooxygenase (indomethacin) or both of these enzyme systems (BW755C; eicosatetraynoic acid, ETYA) on the release of beta-endorphin-like (beta-E-IR) and adrenocorticotropin-like immunoreactivity (ACTH-IR) from rat anterior pituitary quarters incubated in vitro. NDGA and ETYA did not influence the basal release of beta-E- and ACTH-IR. However, upon stimulation by arginine-vasopressin (AVP) or synthetic ovine corticotropin-releasing factor (CRF(1-41], NDGA inhibited beta-E-IR release by 40%. ETYA inhibited AVP-induced release of beta-E- and ACTH-IR by 75%. Indomethacin and BW755C (lower concentration) enhanced beta-E-IR release, induced by AVP, by about 100%, whereas BW755C (higher concentration) had no effect. When indomethacin was present, NDGA, ETYA and BW755C (higher concentration) inhibited AVP-induced release of beta-E- and ACTH-IR. Prostaglandin E2 (PGE2) inhibited beta-E-IR release in response to AVP but failed to do so in the presence of NDGA. 12-OH-5,8,10,14-eicosatetraenoic acid (12-HETE) had no effect. When anterior pituitary quarters were incubated with 3H-arachidonic acid (3H-AA), NDGA and BW755C (higher concentration) but not indomethacin and BW755C (lower concentration) blocked the formation of a metabolite which co-migrated with 12-HETE on thin-layer chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-endorphin and adrenocorticotropin release from rat adenohypophysis in vitro: evidence for local modulation by arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathway. 609 88

Neurotensin (NT) elevates leukotriene levels in animals and stimulates 5-HETE formation in prostate cancer PC3 cells. PC3 cell growth is stimulated by NT and inhibited by lipoxygenase (LOX) blockers. This led us to test LOX blockers (NDGA, MK886, ETYA, Rev5901, AA861 and others) for effects on NT binding and signaling. LOX blockers dramatically enhanced 125I-neurotensin binding to NT receptor NTR1 in PC3 cells, whereas they inhibited NT-induced inositol phosphate formation. These effects were indirect (binding to isolated membranes was unaffected), receptor-specific (binding to beta2-adrenergic, V1a-vasopressin, EGF and bombesin receptor was unaffected) and pathway-specific (cyclooxygenase inhibitors were inactive). NT receptor affinity was increased but receptor number and % internalization were unchanged. Also supporting the involvement of arachidonic acid metabolism in NTR1 regulation was the finding that inhibitors of PLA2 and DAG lipase enhanced NT binding. These findings suggest that NTR1 is regulated by specific feedback mechanism(s) involving lipid peroxidation and/or LOX-dependent processes.
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PMID:Regulation of neurotensin receptor function by the arachidonic acid-lipoxygenase pathway in prostate cancer PC3 cells. 1640 49

The objective of this study was to determine whether arachidonate metabolites are involved in the vasoconstrictive effects of angiotensin II in rats. In the isolated perfused heart, dexamethasone (4 mg/kg) significantly suppressed the maximal decreases in coronary flow induced by angiotensin II and vasopressin (reference drug). In the heart, the nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1 muM) markedly suppressed the angiotensin II-induced decreases in coronary flow. NDGA (10 muM) inhibited both angiotensin II- and methoxamine- (reference drug) induced contractions in aortic rings with (in the presence of L-NAME) and without endothelium. In the heart, the leukotriene synthesis inhibitor MK-886 (0.3 muM) significantly reduced the maximal effects to angiotensin II, but the leukotriene antagonist FPL 55712 (0.1 and 0.3 muM) had no effect. We conclude that in the isolated perfused rat heart angiotensin II-induced decreases in coronary flow are in part mediated by Hpoxygenase products, which might be derived from the 5-Hpoxygenase pathway, but are probably not leukotrienes. Furthermore, endothelium independent Hpoxygenase products mediate part of the contractile responses to angiotensin II in the isolated rat aorta.
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PMID:Role of lipoxygenase products in the effects of angiotensin II in the isolated aorta and perfused heart of the rat. 1847 74