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)

The de novo pyrimidine synthetic enzyme, aspartate carbamyltransferase, and the two pyrimidine salvage enzymes, uridine and thymidine kinases, of the rat testis and epididymis were measured 1, 2, 4, 6, 8, and 10 wk following unilateral vasectomy. Vasectomy had no effect on organ wet weights and on testicular and epididymal asparate carbamyltransferase and thymidine kinase activities. Increases in the uridine kinase activity of the caput epididymidis at 2 wk and of the cauda epididymidis from the second to the sixth weeks were the only significant enzymatic changes observed.
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PMID:Pyrimidine synthetic enzymes of the rat testis and epididymis following unilateral vasectomy. 22 15

MTP-1307, 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H- thiopyrano[3,2-d]pyrimidine dimaleate, is a novel oral hypoglycemic agent, structurally different from any existing hypoglycemic drugs. In fasted rats, the hypoglycemic effect of MTP-1307 was accompanied by elevation of the plasma insulin. In glucose tolerance tests, MTP-1307 suppressed the hyperglycemia after glucose loading and significantly enhanced the glucose-induced insulin secretion. In isolated hepatocytes from fasted rats, MTP-1307 inhibited gluconeogenesis from lactate and alanine. Furthermore, MTP-1307 increased the lactate/pyruvate ratio but did not increase the lactate level. MTP-1307 did not influence glycogenolysis in isolated hepatocytes from fed rats. In genetically diabetic ob/ob mice, MTP-1307 decreased the blood glucose level and improved glucose tolerance, but did not affect the level of plasma insulin. MTP-1307 increased 14CO2 production from glucose in isolated epididymal fat pads of ob/ob mice. Thus, these findings suggest that MTP-1307 produces hypoglycemic activities not only in normal animals but also in genetically diabetic animals, and that the hypoglycemic mechanism of MTP-1307 involves the promotion of glucose utilization in adipose tissue and, partially, the inhibition of gluconeogenesis in the liver and the stimulation of insulin release from the pancreas.
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PMID:Pharmacological studies on the hypoglycemic effect of 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H-thi opyrano [3,2-d] pyrimidine dimaleate (MTP-1307), a novel hypoglycemic agent. 266 87

1. Exogenous adenosine triphosphate (ATP) stimulated the short circuit current (SCC) in primary monolayer cultures of rat epididymal cells when added to the apical but not to the basolateral side of the monolayers. Half-maximal stimulation was achieved at 5 x 10(-8) M ATP. 2. The increase in SCC induced by ATP was dependent on the presence of extracellular Cl in the bathing solutions. 3. The effects of other adenosine derivatives, and purine and pyrimidine nucleotides were studied. Their orders of potency in stimulating SCC were: ATP greater than adenosine diphosphate much greater than adenosine monophosphate, adenosine, and ATP greater than inosine triphosphate greater than guanosine triphosphate greater than cytidine triphosphate. These results indicate that ATP interacts with a P2-purinoceptor at the apical membrane of the epididymal cells. 4. The SCC response to ATP was not blocked by 8-phenyltheophylline, a P1-purinoceptor antagonist or by propranolol. Although pretreatment of the cultures with piroxicam abolished the SCC response to bradykinin, it did not affect the response to ATP. This indicates that the SCC response to ATP was not mediated by an increase in the synthesis of prostaglandins. 5. Serosal to mucosal Cl flux (Js-m Cl) and net water flux were measured in the luminally perfused rat epididymis in vivo. ATP (1 microM) added to the luminal perfusion solution caused an increase in Js-m Cl and net water secretion by the epididymal duct. 6. Since spermatozoa contain a high concentration of ATP, it is proposed that ATP released from spermatozoa may affect anion and fluid secretion by the epididymis. The control of secretion via the apical purinoceptors offers a means by which spermatozoa regulate the fluidity of their own environment.
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PMID:Control of anion and fluid secretion by apical P2-purinoceptors in the rat epididymis. 321 90

Cancer cachexia, characterized by weight loss and progressive tissue wasting, has been postulated to be mediated by cytokines. In this study the effect of FR143430, (2-(4-fluorophenyl)-4, 5, 6, 7-tetrahydro-3-(4-pyridyl)pyrazolo[1, 5-a]pyrimidine monohydrochloride), an inhibitor of Interleukin-1 and Tumor necrosis factor-a (TNF- a), on adenocarcinoma colon26-induced cachexia was investigated in mice. Tumor growth was not affected. Nevertheless, treatment with FR143430 (0.1 to lmg) into the tumor resulted in the attenuation of the reduction in body weight, food intake, epididymal fat and carcass weight, the decrease in the circulating levels of triglyceride and glucose, and the increase in the circulating levels of total cholesterol, non esterified free fatty acid (NEFA) and total protein, which were induced by the presence of the tumor. However, oral treatment with FR143430 failed to show an inhibitory effect on cachexia induction. Overall, this study demonstrated that the cachexia induced by colon26 was alleviated by the injection of FR143430 into the tumor in sufficient quantity, without any effect on tumor growth, suggesting the potential utility of cytokine suppressive agents e for the treatment of cancer cachexia.
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PMID:Effect of FR143430, a novel cytokine suppressive agent, on adenocarcinoma colon26-induced cachexia in mice. 956 68

The effect of nucleoside on Na+ reabsorption via Na+/nucleoside cotransporter in cultured rat epididymal epithelia was studied by short-circuit current (Isc) technique. Guanosine added apically stimulated Isc in a dose-dependent manner, with a median effective concentration (EC50) of 7 +/- 2 microM (mean +/- SEM). Removal of Na+ from the apical bathing solution or pretreatment with a nonspecific Na+/nucleoside cotransporter inhibitor, phloridzin, completely blocked the Isc response to guanosine. Moreover, the guanosine response was abolished by pretreatment of the tissue with ouabain, a Na+/K+-ATPase inhibitor, suggesting the involvement of Na+/nucleoside cotransporter on the apical side and Na+/K+-ATPase on the basolateral side in Na+ reabsorption. In contrast, the Isc response to guanosine was not affected after desensitization of purinoceptors by ATP. Addition of the Na+/K+/2Cl- symport inhibitor bumetanide to the basolateral side or the nonspecific Cl- channel blocker diphenylamine-2-carboxylate to the apical side showed no effect on the Isc response to guanosine, excluding stimulation of Cl- secretion by guanosine as the cause of the guanosine-induced Isc. The Isc response to purine nucleoside (guanosine and inosine) was much higher than that to pyrimidine nucleoside (thymidine and cytidine). Consistent with substrate specificity, results of reverse transcription-polymerase chain reaction revealed mRNA for concentrative nucleoside transporter (CNT2), which is a purine nucleoside-selective Na+/nucleoside cotransporter in the epididymis, but not for CNT1. It is suggested that the Na+/nucleoside cotransporter (i.e., CNT2) may be one of the elements involved in Na+ and fluid reabsorption in the epididymis, thereby providing an optimal microenvironment for the maturation and storage of spermatozoa.
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PMID:Na+ reabsorption in cultured rat epididymal epithelium via the Na+/nucleoside cotransporter. 1120 89

The nucleoside transport systems in cultured epididymal epithelium were characterized and found to be similar between the proximal (caput and corpus) and distal (cauda) regions of the epididymis. Functional studies revealed that 70% of the total nucleoside uptake was Na(+) dependent, while 30% was Na(+) independent. The Na(+)-independent nucleoside transport was mediated by both the equilibrative nitrobenzylthioinosine (NBMPR)-sensitive system (40%) and the NBMPR-insensitive system (60%), which was supported by a biphasic dose response to NBMPR inhibition. The Na(+)-dependent [(3)H]uridine uptake was selectively inhibited 80% by purine nucleosides, indicating that the purine nucleoside-selective N1 system is predominant. Since Na(+)-dependent [(3)H]guanosine uptake was inhibited by thymidine by 20% and Na(+)-dependent [(3)H]thymidine uptake was broadly inhibited by purine and pyrimidine nucleosides, this suggested the presence of the broadly selective N3 system accounting for 20% of Na(+)-dependent nucleoside uptake. Results of RT-PCR confirmed the presence of mRNA for equilibrative nucleoside transporter (ENT) 1, ENT2, and concentrative nucleoside transporter (CNT) 2 and the absence of CNT1. It is suggested that the nucleoside transporters in epididymis may be important for sperm maturation by regulating the extracellular concentration of adenosine in epididymal plasma.
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PMID:Characterization of nucleoside transport systems in cultured rat epididymal epithelium. 1128 19

Monascus-fermented rice has been used to treat digestive disorder and promote blood circulation in China and other Asian countries for centuries. However, the effects and mechanisms of Monascus purpureus-fermented common buckwheat (HQ) on non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are unclear. Here, oral supplementation of HQ significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated some biochemical parameters of serum and liver related to lipid metabolism in mice fed a high-fat and high-cholesterol diet (HFD). Histological analysis also showed that the excessive accumulation of lipid droplets in the livers induced by HFD-feeding was greatly alleviated by HQ supplementation. Metagenomic analysis revealed that HQ supplementation made significant structural changes in the intestinal microflora of mice fed with HFD. The Spearman's correlation analysis revealed that physiological index, serum and liver lipid profiles were positively correlated with Bacteroidales S24-7, Streptococcus, Allobaculum, and Clostridiales XIII, but negatively associated with Lactobacillus, Ruminococcaceae_NK4A214 group, Ruminiclostridium, and Alistipes. UPLC-QTOF/MS-based liver metabolomics demonstrated that HQ intervention had significant regulatory effects on the metabolic pathways of primary bile acid biosynthesis, pyrimidine metabolism, ether lipid metabolism, glutathione metabolism, glycine, serine and threonine metabolism, and amino sugar and nucleotide sugar metabolism, etc. Additionally, HQ intervention regulated the mRNA levels of hepatic genes involved in hepatic lipid metabolism and bile acid homeostasis. Collectively, these findings present new evidence supporting that HQ has the potential to ameliorate dyslipidemia and NAFLD via modulating the intestinal microbial populations and hepatic metabolite profile in hyperlipidemic mice induced by HFD.
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PMID:Monascus purpureus-fermented common buckwheat protects against dyslipidemia and non-alcoholic fatty liver disease through the regulation of liver metabolome and intestinal microbiome. 3284 89