Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several non-steroidal anti-inflammatory agents (NSAIA) are shown to inhibit the net production of prostaglandin (PG)- like activity from arachidonic acid by a cell-free preparation of guinea-pig lung. Moreover, these agents also antagonize PGE-1-induced contractions of the isolated gerbil colon. The anti-spasmogenic effects are reversible and specific. At high concentrations, indomethacin and mefenamic acid interfere with the binding of PGE-1 to a broken cell preparation of rat epididymal adipocytes. Taken together the data indicate that NSAIA interact with prostaglandins at multiple sites and are consistent with the suggestions reported previously that NSAIA may have multiple in vivo actions.
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PMID:Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents. 113 91

7-oxa-13-prostynoic acid (OPA) and polyphloretin phosphate (PPP) are believed to act as specific antagonists of prostaglandin action. In order to estimate their specificity, the inhibitory effects of these drugs were tested on the activity of adenylate cyclase from several tissues which were stimulated by prostaglandins and several other compounds. In adenylate cyclase preparation from L-fibroblasts both OPA (0.15-1.5 MM) and PPP (0.01-1.0 MG/ML) antagonized not only the stimulatory effects of PGE but also the stimulatory effects of sodium fluoride and increased enzyme activity due to the previous treatment of cell cultures by cholera toxin. Both OPA and PPP produced a dose dependent depression of adenylate cyclase activity to zero values both under basal conditions and after stimulation by sodium fluoride and various hormones in all preparations studied, including rat liver, heart, brain, epididymal adipose tissue, small intestine, renal cortex and renal medulla. The present results indicate that both prostaglandin antagonists may, in higher concentrations, act as nonspecific inhibitors of the catalytic unit of adenylate cyclase rather than specific antagonists of the prostaglandin effects on adenylate cyclase.
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PMID:7-oxa-13-prostynoic acid and polyphloretin phosphate as non-specific antagonists of the stimulatory effects of different agents on adenylate cyclase from various tissues. 123 93

Viprostol, a novel prostaglandin E2 congener, was assessed for in vitro antilipolytic activity in the spontaneously obese rat. In isolated epididymal adipocytes, viprostol exhibited a dose-dependent inhibition of catecholamine-stimulated lipolysis at concentrations ranging from 10 microM to 1 mM, but was ineffective at lower concentrations. Additionally, viprostol exhibited approximately 50% of the antilipolytic activity of naturally-occurring PGE1 and PGE2 at similar concentrations, but was as potent as PGF2 alpha. At 10 microM, viprostol inhibited maximum catecholamine-stimulated lipolysis by approximately 35% of the total, hormone-stimulated glycerol release. The results of these experiments indicate that viprostol exhibits antilipolytic activity in vitro, but is less potent than the naturally-occurring PGE's to which it is most closely related structurally.
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PMID:Antilipolytic activity of viprostol, a transdermally active antihypertensive PGE2 analog. 243 24

In 56 males, vasectomized 8 years previously, and in 56 age-matched non-vasectomized controls, a number of secretory products of prostatic, seminal vesicular and epididymal/testicular origin were used to monitor post-operative changes in accessory sex gland function. Significant reductions were observed in seminal plasma volume (3.0 vs 4.9 ml, P less than 0.01), and the total ejaculate contents of zinc (5.1 vs 9.7 mumol, P less than 0.01), magnesium (10.6 vs 26.5 mumol, P less than 0.01), PAP (371 vs 1260 IU, P less than 0.005) and citric acid (76.7 vs 127.9 mumol, P less than 0.05), indicating a major impact on secretions of prostatic origin. Unaltered PGE-1 (54.3 vs 53.2 micrograms, P less than 0.95) and fructose (3.9 vs 4.5 mumol, P greater than 0.1) indicated no effects on the secretory function of the seminal vesicles. A marked reduction was demonstrated in the ejaculatory contents of the polyamines, spermidine (366 vs 650 nmol, P less than 0.005) and spermine (5435 vs 11 804 nmol, P less than 0.05) but not their acknowledged precursor, putrescine, which is also of prostatic origin.
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PMID:Polyamines and other accessory sex gland secretions in human seminal plasma 8 years after vasectomy. 262 11

Acidic lipids with smooth muscle-stimulating properties were extracted from rat epididymal fat pads and were shown to co-chromatograph with (PGE1) prostaglandin E1, PGE2, and PGF2alpha. Further chemical identification was not possible with the small amounts of material available. A basal efflux of PGE and PGF compounds was observed following incubation of adipose tissue in vitro. Increased efflux of PG was detected under conditions reported to enhance free fatty acid release, i.e., addition of lipolytic hormones or drugs to the incubating medium, prior fasting of the animal, or stimulation of the epididymal nerve. These results, together with a decreased release of PG-like material in the presence of insulin, suggested that the efflux may be associated with lipolysis resulting from activation of a hormone-sensitive lipase. Since the PGs are known to affect the concentration of cyclic adenosine 3', 5'-monophosphate in adipose tissue, and this nucleotide is an intermediary in hormone-stimulated lipolysis, it is possible that the PGs released may serve to maintain the homeostasis of adipose tissue by way of a physiological feedback control mechanism.
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PMID:Release of prostaglandin from rat epididymal fat pad on nervous and hormonal stimulation. 429 86

Incremental levels of trilinoelaidate (tt18:2) were fed to rats for 11 weeks and changes in lung and epididymal lipid fatty acid composition were determined, and concentrations of prostanoids in serum, lung and stomach fundus were measured. Platelet aggregation to various agonists was tested. In the lung there was a concomitant increase of linoelaidate corresponding to incremental dietary levels in all lipid classes (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine-phosphatidylinositol and neutral lipids). Arachidonic acid in lung phosphatidylcholine was markedly decreased. Epididymis accumulated linoelaidate in only the neutral lipid fraction; no tt18:2 was found in any of the phospholipid classes. Serum prostanoid levels (thromboxane B2 and prostaglandins PGF2 alpha and PGE) were significantly decreased in rats fed high levels of tt18:2, but were not altered at lower levels of consumption; the concentrations of 6-keto-PGF1 alpha were not significantly altered at any level of tt18:2. Platelet responsiveness to various agonists was not significantly altered by incremental dietary trilinoelaidate, i.e., ADP, thrombin, collagen and calcium elicited similar aggregation responses. In conclusion, dietary trilinoelaidate at low levels of consumption, while being incorporated into various lipid classes, did not alter serum and tissue prostanoid levels or markedly affect platelet aggregation.
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PMID:Dietary trilinoelaidate: effects on organ fatty acid composition, prostanoid biosynthesis and platelet function in rats. 669 85

There is a correlation between circulating insulin levels and blood pressure over a wide range of insulin levels and in a variety of clinical conditions. Production of prostaglandin (PG)E(2) (PGE(2)) and prostacyclin (PGI(2)), two potent vasodilators, by adipose tissue is increased in severe insulin deficiency, eg, diabetic ketoacidosis (DKA), explaining the decreased peripheral vascular resistance in DKA. Conversely, decreased production of PGE(2) and PGI(2) may mediate the relationship between hyperinsulinemia and hypertension. Although insulin inhibits PG production in normal rat adipose tissue, PG production in adipose tissue from patients or experimental animals with nonketotic diabetes mellitus (DM) and DKA has not been studied. We examined the effect of plasma insulin levels on blood pressure and on adipose tissue PG production in rats with DM and DKA and normal rats. There was a significant relationship between plasma insulin level and blood pressure in rats with DM and normal controls (P < .021) and in rats with DKA and normal controls (P < .0001). There was an inverse linear correlation between plasma insulin levels and basal 6-keto-PGF(1 alpha) production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue in rats with DKA and normal rats (P < .0252, R2 = .67). Rates of basal glycerol, PGE(2), and 6-keto-PGF(1alpha) production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue were significantly higher in rats with DKA than in normal rats. These rates were also higher in rats with DM than in normal rats, but only glycerol values were statistically significant. In rats with DM, PGE(2) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of 6-keto-PGF(1alpha) was not stimulated. In rats with DKA, 6-keto-PGF(1alpha) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of PGE(2) was not stimulated. We conclude the following: (1) there is a close correlation between circulating insulin level and systemic blood pressure when rats with DM and DKA are compared with controls; (2) in insulin deficiency, PGI(2) and PGE(2) production are increased in adipose tissue versus normal tissue; and (3) the correlation between insulin level and blood pressure may be mediated by the inhibitory effect of insulin on vasodilative PG production by adipose tissue.
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PMID:The relationship between plasma insulin level, prostaglandin production by adipose tissue, and blood pressure in normal rats and rats with diabetes mellitus and diabetic ketoacidosis. 863 42

Although a number of prostaglandin E(2) (PGE(2)) receptor subtypes have been cloned, limited studies have been performed to elucidate subtypes that subserve specific actions of this eicosanoid, in part because of a paucity of selective receptor antagonists. Using reverse transcription-polymerase chain reaction (PCR) and antisense oligonucleotides, we examined which prostaglandin E(2) receptor (EP receptor) subtypes are expressed in sensory neurons and which mediate the PGE(2)-induced increase in cAMP production and augmentation of peptide release. Reverse transcription-PCR of cDNA isolated from rat sensory neurons grown in culture revealed PCR products for the EP1, EP2, EP3C, and EP4 receptor subtypes but not the EP3A or EP3B. Preexposing neuronal cultures for 48 h to antisense oligonucleotides of EP3C and EP4 mRNA diminished expression of the respective receptors by approximately 80%, abolished the PGE(2)-stimulated production of cAMP, and blocked the ability of PGE(2) to augment release of immunoreactive substance P and calcitonin gene-related peptide. Pretreating with individual antisense against the EP2, EP3C, or EP4 receptors or combinations of missense oligonucleotides had no effect on PGE(2)-induced activity. Treatment with antisense to EP3C and EP4 receptor subtypes did not alter the ability of forskolin to increase cAMP or enhance peptide release. These results demonstrate that sensory neurons are capable of expressing multiple EP receptor subtypes but that only the EP3C and EP4 receptors mediate PGE(2)-induced sensitization of sensory neurons.
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PMID:Prostaglandin receptor subtypes, EP3C and EP4, mediate the prostaglandin E2-induced cAMP production and sensitization of sensory neurons. 1127

The epididymal portion of the rat vas deferens produced prostaglandins (PG) E(2), F(2alpha)and 6-keto F(1alpha). Electrical stimulation (ES, 0.1 Hz, 1 ms) increased such production by 100%, and similar results were obtained in the presence of 1.0 microM bradykinin (Bk). When both stimuli were applied simultaneously, the increases in PG production were 1100% for PGE(2), 800% for PGF(2alpha)and 400% for PG6-keto F(1alpha). Prazosin abolished the effect of ES on PG production. A selective Bk B(2)-receptor antagonist abolished the increase in PG production induced by Bk, both in non-stimulated and in ES tissues. Bk (1.0 microM) elicited contractile responses in non-stimulated as well as in ES tissues, responses that were not modified in the presence of 10 microM indomethacin. In conclusion, the effects of Bk on prostaglandin production appears to depend on the activation of B(2) receptors, while the increase in prostaglandin release induced by ES, and the effects observed with both stimuli simultaneously, should be mediated by the release of noradrenaline and the subsequent activation of alpha(1) adrenoceptors.
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PMID:Bradykinin and electrical stimulation increase prostaglandin production in the rat vas deferens. 1148 2

Previous work has suggested that functional interrelationships may exist between inhibition of insulin secretion by interleukin (IL)-1beta and the endogenous synthesis of prostaglandin E(2) (PGE(2)) in the pancreatic islet. These studies were performed to ascertain the relative abundance of E prostaglandin (EP) receptor mRNAs in tissues that are major targets, or major degradative sites, of insulin; to identify which EP receptor type mediates PGE(2) inhibition of insulin secretion in pancreatic islets; and to examine possible sites of action through which sodium salicylate might affect IL-1beta/PGE(2) interactions. Real-time fluorescence-based RT-PCR indicated that EP3 is the most abundant EP receptor type in islets, liver, kidney, and epididymal fat. EP3 mRNA is the least, whereas EP2 mRNA is the most, abundant type in skeletal muscle. Misoprostol, an EP3 agonist, inhibited glucose-induced insulin secretion from islets, an event that was prevented by preincubation with pertussis toxin, by decreasing cAMP. Electromobility shift assays demonstrated that sodium salicylate inhibits IL-1beta-induced nuclear factor-kappaB (NF-kappaB) activation. Sodium salicylate also prevented IL-1beta from inducing EP3 and cyclooxygenase (COX)-2 gene expression in islets and thereby prevented IL-1beta from inhibiting glucose-induced insulin secretion. These findings indicate that the sites of action through which sodium salicylate inhibits these negative effects of IL-1beta on beta-cell function include activation of NF-kappaB as well as generation of PGE(2) by COX-2.
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PMID:Inhibition of interleukin-1beta-induced COX-2 and EP3 gene expression by sodium salicylate enhances pancreatic islet beta-cell function. 1203 64


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