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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain biochemical parameters of acute liver injury induced by carbon tetrachloride were investigated in rats treated with prostacyclin (PGI2) and two of its derivatives. Serum glutamate oxalacetate transaminase elevation and both triglyceride accumulation and reduction of glycogen content in liver were significantly suppressed by PGI2, 7-oxo-PGI2, and 20-methyl-13,14-didehydro-2,4-m-interphenylene-PGI2 48 hr after the injury. Prostacyclins partially restored some of the parameters of injury even in doses of 10 micrograms/kg ip. When the compounds were given 24 hr after CCl4 intoxication, much more pronounced protection was observed than in the case of treatments 1 hr before administration of the hepatotoxin. Thus, all tested prostacyclins exerted significant protective effects on acute liver damage which is obtained mainly in the second phase of the injury.
Exp Mol Pathol 1985 Apr
PMID:Hepatoprotective effects of prostacyclins on CCl4-induced liver injury in rats. 388 60

Homogenates of control and diet-induced atherosclerotic aortas of rabbit were prepared and the levels of DNA, protein, free and esterified cholesterol, and six enzymes known to be associated with various subcellular organelles [N-acetyl-beta-glucosaminidase, beta-galactosidase (lysosomes); cytochrome oxidase (mitochondria); neutral alpha-glucosidase (endoplasmic reticulum); 5'-nucleotidase (plasma membrane); catalase (peroxisomes)] were compared between control and atherosclerotic preparations. The levels of prostaglandins I2, E2, and F2 alpha, based on DNA, also were measured by radioimmunoassay. Atherosclerotic aortas were significantly enriched in catalase activity (440%) and in each of the acid hydrolases (395 and 630%), based on DNA, as well as in free (630%) and esterified cholesterol (930%), based on tissue wet weight, compared to control aortas. The control level of prostaglandin I2 was 10-fold higher than that of prostaglandin E2, which was 3-fold higher than that of prostaglandin F 2 alpha. Prostaglandin I2 doubled in amount with advanced atherosclerosis, while prostaglandin E2 increased over 10-fold, resulting in twice the amount of prostaglandin I2 than E2 in advanced atherosclerosis; the level of prostaglandin F2 alpha did not appear to change significantly with atherosclerosis. Increased levels of prostaglandins I2 and E2 were correlated significantly with increased aortic total cholesterol content (based on DNA) but not increased serum cholesterol levels. N-Acetyl-beta-glucosaminidase activity also was correlated significantly to aortic total cholesterol content and beta-galactosidase activity, as well as to the level of prostaglandin I2; in contrast, N-acetyl-beta-glucosaminidase was not significantly correlated to prostaglandin E2. The association of prostaglandins I2 and E2 with aortic total cholesterol suggests the participation of prostaglandins in the response of arterial cells to lipid accumulation in atherosclerosis. The specific association of aortic prostaglandin I2 level and N-acetyl-beta-glucosaminidase activity further suggests a possible role for this prostaglandin during arterial intralysosomal cholesterol accumulation.
Exp Mol Pathol 1985 Aug
PMID:Arterial prostaglandins and lysosomal function during atherogenesis. I. Homogenates of diet-induced atherosclerotic aortas of rabbit. 389 3

This report validates and expands further the interpretation of our findings on prostaglandins and lysosomes in rabbit aortic homogenates (see paper I of this series) to enzymatically isolated and separated aortic cell populations during atherogenesis. Evidence is provided by which isolated arterial cells may be considered representative of in situ increases of diseased aortic tissue prostaglandin I2 and E2 levels, as well as lysosomal acid hydrolase activities and total cholesterol content based on DNA. Increasing latency of aortic lysosomal N-acetyl-beta-glucosaminidase activity was confirmed and correlated with increasing severity of atherosclerosis, in parallel to increasing levels of prostaglandin I2 but not increasing levels of prostaglandin E2. Ultrastructural observations also confirmed aortic intracellular lipid accumulation within lysosomes and as lipid droplets. Consistent with these relationships, separated low density, lipid-filled aortic cells were especially increased in total (197%) and latent (15%) lysosomal acid hydrolase activities, catalase activity (274%), total cholesterol (151%), and in both prostaglandin I2 (67%) and E2 (325%) levels based on DNA, as compared to control aortic cells or more normal-appearing high-density diseased aortic smooth muscle cells; high-density diseased aortic cells were increased in prostaglandin E2 but similar in latent acid hydrolase activity compared to control aortic cells. Since the total cholesterol content of rabbit atherosclerotic aortas was evidenced more intracellularly (75%) than extracellularly (25%) in this study, the association of increased prostaglandin I2 and E2 levels with low-density lipid-filled cells suggest the participation of these prostaglandins in the genesis of aortic foam cells during arterial lipid accumulation in rabbit atherosclerosis. The association of increasing prostaglandin I2 levels and increasing latent lysosomal N-acetyl-beta-glucosaminidase activities also implicates a possible relationship between this prostaglandin and lysosomal membranes of aortic cells, either primary or secondary to intralysosomal lipid accumulation.
Exp Mol Pathol 1985 Aug
PMID:Arterial prostaglandins and lysosomal function during atherogenesis. II. Isolated cells of diet-induced atherosclerotic aortas of rabbit. 392 57

The role of thrombocytes in the production of isoproterenol-induced cardiac necrosis was investigated in rats rendered thrombocytopenic (A) as well as in rats treated with a prostacyclin analogue (B). According to quantitative morphometric evaluation the area of necrotic tissue amounted to about 1% 9 h following administration of isoproterenol (40 mg/kg). In both groups of treated animals the number and area of necroses were strongly reduced (to 23% group A, to 34% group B, P less than or equal to 0.1 for both groups). In contrast, the reduction of myocardial adenine nucleotide levels induced by isoproterenol was the same (5.06 to 3.57 and 3.60 microM/g wet wt, respectively) in thrombocytopenic and non-thrombocytopenic rats. Quantitative comparison of the fraction of necrotic tissue and of the fraction of lost nucleotides suggests that non-necrotic rather than necrotic tissue predominantly contributes to the reduction of nucleotides. The dependence of cardiac necrosis production on the presence or normal aggregability of platelets points out at platelet-dependent microvascular alterations as a main cause of isoproterenol-induced cardiac necroses.
J Mol Cell Cardiol 1985 Apr
PMID:Essential contribution of thrombocytes to the occurrence of catecholamine-induced cardiac necroses. 402 Aug 76

Adenylate cyclase in plasma membranes was inhibited by micromolar concentrations of delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol and by levonantradol and desacetyllevonantradol. This inhibition was noncompetitive for stimulation of the enzyme at the prostanoid receptor by prostaglandin E1 or prostacyclin, or at the peptide receptor by secretin or vasoactive intestinal peptide. Forskolin-activated adenylate cyclase was also inhibited by cannabimimetic agents. Inhibition by cannabinoid compounds was neither synergistic nor additive with muscarinic or alpha-adrenergic agents when each was present at maximally inhibitory concentrations. Cannabinoid inhibition was not blocked by atropine, yohimbine, or naloxone, suggesting that muscarinic, alpha 2-adrenergic and certain opiate receptors may not be required for the response. The inhibition of adenylate cyclase was specific for psychoactive cannabinoids, since cannabinol and cannabidiol produced minimal or no response. Inhibition was also stereoselective, since dextronantradol did not produce the response. A biphasic log dose-response curve was observed for each of the cannabinoid drugs, such that reversal of the inhibition occurred at 3-10 microM. Possible mechanisms for the effects of cannabinoid drugs on adenylate cyclase activity are discussed.
Mol Pharmacol 1984 Nov
PMID:Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. 609 1

In spontaneously atherosclerosis-susceptible White Carneau pigeons intimal cushions are noted consistently at the coeliac branch of aorta at birth. While these cushions do not progress into atherosclerotic lesions, the area across from the cushion (so called "lesion area") develop a classic atherosclerotic plaque by three years of age. In order to explain this regional aortic susceptibility to atherosclerosis, cholesterol and cholesteryl ester concentrations and prostaglandin biosynthesis in the two aortic regions were examined. It was found that the concentration of free and esterified cholesterol was higher in the intimal cushion area. Examination of the formation of various prostaglandins from C14-arachidonic acid indicates a striking increase in PGE2 synthesis in the lesion area with no difference in the formation of 6-keto PGF1 alpha (stable product of PGI2). These studies suggest that one of the earliest changes noted in the "lesion area" that differs from the intimal cushion is the enhanced formation of PGE2.
Virchows Arch B Cell Pathol Incl Mol Pathol 1981
PMID:Regional aortic differences in atherosclerosis susceptibility. Relationship to lipid concentration and prostaglandin biosynthesis. 611 22

[3H]PGE2 specifically bound to isolated glomeruli. The KD value and the number of sites were 80 nM and 528 fmoles/mg respectively. PGE1 and PGE2 resulted in equipotent inhibition of binding whereas PGI2 was markedly less active. It was not possible to demonstrate specific receptors for PGE2 in glomerular mesangial and epithelial cultured cells. PGE1, PGE2 and PGI2 (0.1-100 microM) stimulated cyclic AMP concentration both in isolated glomeruli and glomerular cultured cells. Basal cyclic AMP in epithelial cells was greater than in mesangial cells or glomeruli. The cyclic AMP accumulation in the presence of PGs was greatest in mesangial cells. Maximum stimulation was in the range 300-1400%. For the three preparations, PGE2 and PGE1 produced a greater effect than PGI2. ED50 values were identical for PGE1 and PGE2 (5 microM for epithelial cells and glomeruli, 20 microM for mesangial cells). ED50 value for PGI2 were lower than those for PGE1 or PGE2 (0.2, 2 and 5 microM for glomeruli, epithelial cells and mesangial cells, respectively). The effects of the three PGs were not additive when tested at maximally effective concentrations. These results demonstrate that PGE1, PGE2 and PGI2 stimulate glomerular and cellular cyclic AMP. A relationship between [3H]PGE2 binding sites and this biological effect has not been established. The physiological events secondary to the increase in glomerular cyclic AMP are also yet to be determined.
Mol Cell Endocrinol 1983 May
PMID:PGE2 binding sites and PG-stimulated cyclic AMP accumulation in rat isolated glomeruli and glomerular cultured cells. 613 4

Prostacyclin (PGI2) can protect the heart against ischemia, i.e. it can reduce myocardial damage [9, 10]. PGI2 protects the myocardium in vivo by preventing platelets from clumping and by dispersing preformed platelet aggregates [1,14]. However, also in the absence of platelets, PGI2 was shown to protect the myocardium against ischemia at concentrations that did not affect smooth muscle tone in the vessel wall [2]. This protective effect of PGI2 in vitro might be related to a stabilization of cell membranes in adrenergic nerve endings and hence to the prevention of ischemia-induced catecholamine release [13]. The instability of PGI2, both in vitro and in vivo, limits its application during long ischemic periods. Recently, a stable prostacyclin analogue, ZK 36 374, was demonstrated to have several prostacyclin-mimetic activities, both in vitro and in vivo [11,12]. In this communication we report upon the beneficial effect of this stable prostacyclin analogue at a low concentration (4 nM) on the extent of ischemic damage, on the recovery of myocardial function and on the occurrence of arrhythmias in the isolated rat heart after 24 h hypothermic cardiac arrest.
J Mol Cell Cardiol 1983 Nov
PMID:Improved functional recovery of the isolated rat heart after 24 hours of hypothermic arrest with a stable prostacyclin analogue (ZK 36 374). 619 28

Prostaglandin (PGE2, PGF2 alpha) production by bovine fasciculo-reticulata adrenocortical cell suspensions was examined using specific radioimmunoassay procedures. No detectable PGs (greater than 50 pg) could be measured in the extract from up to 2 x 10(6) cell incubations after 1 h, with or without the presence of ACTH, although these cells expressed full steroidogenic capabilities under these conditions. The same preparations could produce PGs when supplemented with arachidonic acid but ACTH had no effect on this process. These negative findings could not be explained by analytical artifacts or metabolic transformation. However, an active PG synthetase system was characterized in bovine adrenocortical subcellular preparations. This system converted arachidonate and endogenous substrate(s) to PGE2 as the major product. No thromboxane or prostacyclin pathways were detected even at high enzyme/substrate ratio. Although the microsomal adrenal cortex PG synthetase activity shares many features with those observed in other tissues (Km = 8.3 x 10(-5) M, optimal pH at 8.0, stimulation of PGE2 formation in the presence of glutathione and L-epinphrine), its specific activity was comparatively low (Vmax = 2.5 ng PGE2/min/mg microsomal proteins), which may explain our negative findings using cell suspensions. These findings do not provide evidence to support the hypothesis proposing a role of endogenous PGs in the mechanism of acute ACTH action in the case of bovine adrenal cortex.
Mol Cell Endocrinol 1980 Jun
PMID:Prostaglandin synthetase activity in bovine adrenocortical cells and subcellular preparations: effect of ACTH. 624 99

Exposure of the oestrogen-dominated rat myometrium to either isoproterenol or PGE2 resulted in a rapid but transient accumulation of cyclic AMP, with a progressive loss of responsiveness to the corresponding agonist. Induction of refractoriness was a time- and dose-related phenomenon. In the earliest time, desensitization was agonist-specific but was followed, with continued exposure, by a cross desensitization between isoproterenol and PGE2 and vice versa. Differential time courses for development and reversal of specific and heterologous refractoriness indicate at least 2 different processes for the 2 phenomena, the non-specific type being possibly mediated by cyclic AMP. Exposure to isoproterenol or PGE2 also caused an attenuated cyclic AMP response to prostacyclin (PGI2). Kinetics for PGE2-induced desensitization to PGI2 were comparable to that of an agonist-specific refractoriness, indicating that PGE2 and PGI2 may share common receptor sites. PGF2 alpha, PGD2 and 6-keto PGF1 alpha, which contract the myometrium but are ineffective on adenylate-cyclase activity, did not promote cyclic AMP refractoriness to PGE2, PGI2 or isoproterenol. Isoproterenol also caused refractoriness to its own relaxing activity, whereas PGE2 did not affect isoproterenol-induced relaxation despite a marked attenuation of the beta-adrenergic response to cyclic AMP. These results provide further evidence for the non-exclusive role of cyclic AMP in mediating uterine relaxation.
Mol Cell Endocrinol 1980 Oct
PMID:Modulation of cyclic AMP content of the rat myometrium: desensitization to isoproterenol, PGE2 and prostacyclin. 625 20


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