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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Capillaries isolated by collagenase digestion of hamster epididymal fat pads were used to examine the properties of endothelial adenylate cyclase and cyclic nucleotide phosphodiesterase. Adenylate cyclase activity in capillary homogenates was increased by 10 microM GTP or 100 microM isoproterenol. Lower concentrations of the catecholamine and 5.7 microM prostaglandin E1 did not stimulate endothelial adenylate cyclase activity unless GTP was included in the assay system. The effects of isoproterenol on capillary adenylate cyclase activity were blocked by propranolol, but were not affected by phentolamine. Phosphodiesterase activity in endothelial homogenates showed anomalous kinetic behavior with either cyclic AMP or cyclic GMP as the enzyme substrate. At substrate concentrations below 1 microM, capillary phosphodiesterase activity hydrolyzed cyclic GMP 2-6 times faster than cyclic AMP. However, at high substrate levels, e.g., 100 microM, cyclic AMP and cyclic GMP were degraded at similar rates. Hydrolysis of 1 microM cyclic AMP by capillary homogenates was stimulated by 0.1 and 1 microM cyclic GMP. Caffeine, 1-methyl-3-isobutylxanthine, papaverine and dipyridamole SQ 20009 were effective inhibitors of capillary phosphodiesterase activity. In contrast, imidazole enhanced the activity of the enzyme. The presence of adenylate cyclase and phosphodiesterase activities in hamster isolated capillaries is consistent with a role for cyclic AMP in the regulation of endothelial function. Moreover, the experiments described here indicate that hamster isolated capillaries are useful model systems for studying the metabolism of vascular endothelium.
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PMID:Properties of adenylate cyclase and cyclic nucleotide phosphodiesterase in hamster isolated capillary preparations. 624 1

Effects of Phthalazinol (EG 626), a cyclic AMP phosphodiesterase inhibitor, a thromboxane A2 antagonist and an antiatherosclerotic agent was examined regarding lipolytic enzyme activities in rat epididymal adipose tissue. The effect of Pyridinolcarbamate (Anginin) was concomitantly examined. There was a significant decrease in serum triacylglycerol levels in rats given EG 626 (100-500 mg/kg), p.o. for 1-3 weeks. In adipose tissue from EG 626 treated rats, the basal and adrenalin induced lipolysis, and cholesterylester hydrolase activity were markedly enhanced, while the phosphodiesterase activity was decreased. Anginin treatment had no effect either on the serum lipid levels or the cholesterylester hydrolase activity. An elevation in cholesterylester hydrolase activity and lipolysis by EG 626 was observed both in vivo and in vitro. Incubation of the adipose tissue with 0.229 mM of EG 626 or 0.603 mM of theophylline induced a lipolysis equivalent to that seen with 2.7 x 10(-2) mM of adrenalin. These results indicate that EG 626 exerted marked effects on lipolysis and cholesterylester hydrolase activity, probably through inhibition of phosphodiesterase. Possible contributions of the enhanced cholesterylester hydrolase activities to the antiatherogenic effect were discussed.
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PMID:Effects of phthalazinol (EG 626) and pyridinolcarbamate (Anginin) on lipolytic enzyme activities in rat adipose tissue -in vivo and in vitro-. 624 48

When rats were injected with the progestin ethynodiol diacetate in doses that suppressed spermatogenesis and the growth of accessory sex glands, the level of phosphodiesterase in epididymal and prostate tissues increased 5- to 10-fold. This increase was prevented by concurrent administration of testosterone propionate. A similar increase in phosphodiesterase activity was observed in the epididymides and prostates of castrated animals, with reversal by treatment with androgen. In immature rats approaching puberty, the phosphodiesterase activity in epididymis and prostate increased while the blood testosterone level remained low; as the testosterone level rose with the onset of puberty, the phosphodiesterase activity decreased. Incubation of enzymically active extracts of accessory tissues from castrated rats with heat-treated extracts of the corresponding normal tissues resulted in strong inhibition of the initially high phosphodiesterase activity. The addition of heat-treated extracts of accessory glands from castrated rats to enzymically active extracts of the corresponding tissues from normal rats resulted in a marked elevation of their phosphodiesterase activities. Of the two heat-stable modulators, the inhibitor factor was dialyzable. The dependence of this factor on testosterone suggests a mechanism of action by which the steroid hormone, by inducing the production in its target tissues of an inhibitory modulator of phosphodiesterase, controls the maintenance of functional levels of cAMP.
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PMID:Androgen control of an inhibitory modulator of phosphodiesterase in rat epididymis and prostate. 625 8

Six newly-synthetized 7-N-basically substituted xanthine derivatives were studied for inhibitory action on phosphodiesterase with high Km in homogenates from brain, lung and epididymal fatty tissue. Theophylline is used for comparative purposes. The effect of part of the compounds on lipolysis in vivo is also studied. Some of the newly-synthetized compounds are found to manifest a marked ability to inhibit the enzyme studied in brain and lung homogenates, and compound with code V has equal action to that of theophylline. The newly-synthetized compounds are poor inhibitors of the enzyme in epididymal fatty tissue, unlike theophylline which demonstrates the same inhibitory capacity as in the other homogenates. These data correlate with the results obtained when studying lipolysis. Theophylline in a dose of 50 mg/kg i. p. increases twice the serum content of the free fatty acids, while the newly-synthetized compounds have no effect on it, even when applied in high doses.
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PMID:Influence of newly-synthetized xanthine derivatives on phosphodiesterase with high Km in homogenates of different organs and on lipolysis in vivo. 626 52

The activities of cAMP and cGMP phosphodiesterases (EC 3.1.4.1), adenylate cyclase (EC 4.6.1.1) and protein carboxyl-methylase (EC 2.1.1.24) were measured in the particulate and soluble (105 000 g supernatant) fractions of washed spermatozoa isolated from five segments of the adult rat epididymis. The activities of both phosphodiesterases decreased during epididymal transit, whereas adenylate cyclase and protein carboxyl-methylase underwent a progressive increase, the latter showing the most marked alteration. Both cAMP and cGMP phosphodiesterases as well as the adenylate cyclase were all associated primarily with the particulate fraction, and the extent to which these enzymes were associated with the membranes increased as the spermatozoa passed through the epididymis. Sperm protein carboxyl-methylase activity was, on the other hand, predominantly soluble in all segments of the epididymis. Adenylate cyclase, cAMP phosphodiesterase and protein carboxyl-methylase activities were found predominantly in the sperm tails, whereas cGMP phosphodiesterase was equally distributed between heads and tails. These observations imply that the acknowledged increase in intracellular cAMP levels which occurs in spermatozoa during epididymal transit may be a consequence of both increased synthesis (adenylate cyclase) and reduced hydrolysis (phosphodiesterase).
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PMID:Rat sperm enzymes during epididymal transit. 628 32

Insulin-effects on adenylate cyclase activity, cyclic AMP (cAMP) content and free fatty acid (FFA) accumulation of rat epididymal fat cells were examined under conditions of maximal inhibition of phosphodiesterase by sufficient amounts of theophylline for the purpose of localizing the site of the antilipolytic action of insulin. After brief preincubation of the cells with physiological amounts of insulin in the presence or absence of 0.1 mM adrenalineee, fat cells were homogenized following the addition of theophylline and then further incubated. Under these conditions, small but significant enhancement of adenylate cyclase activity, cAMP content and FFA accumulation by insulin alone was observed, while insulin remarkably inhibited adrenalin-stimulated FFA accumulation, reducing adenylate cyclase activity and cAMP levels. This increase of cAMP content by insulin was only seen 5 or 15 minutes after the addition of theophylline. Furthermore, this insulin effect was also observed in the experiments which were performed in a medium containing high concentrations of albumin (2%). The concomitant accumulation of FFA might have resulted from the stimulation of lipolysis, rather than from the synthesis of FFA, since there was no added glucose in the medium. And finally, the hydrolysis of 14C-tripalmitate by a fraction of the cell homogenate under the presence of theophylline was more extensive after preincubation of the cells with insulin than without insulin. In summary, insulin, which is recognized as a typical antilipolytic hormone, activated adenylate cyclase and increased lipolysis at its physiological concentrations when it alone exerted its effect upon fat cells under the conditions where phosphodiesterase was completely inhibited by theophylline. Accordingly, the present results indicate the bimodal effect of insulin on adenylate cyclase and lipolysis under the presence of theophylline; enhancement when applied alone, and depression with adrenalin. So it is most likely that the "negative synergism" occurs as a net effect when a mild activator acts together competitively with a strong activator toward the same target. These data suggest the fundamental roles of adenylate cyclase systems in the mechanism of lipolysis regulation by insulin.
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PMID:[Insulin action on adenylate cyclase. The effect of insulin on adenylate cyclase of rat fat cells in the presence of theophylline]. 629 96

A calmodulin dependent cyclic nucleotide phosphodiesterase is associated with the head and tailpieces of demembranated rat caudal epididymal sperm. The phosphodiesterase was stimulated two-fold in the presence of Ca2+, while the simultaneous addition of Ca2+ and calmodulin resulted in a four-fold increase in activity. Ca2+ stimulation was abolished if demembranated sperm were extracted with EGTA and was recovered upon the addition of exogenous calmodulin. Micromolar levels of Ca2+ were required for full stimulation. Trifluoperazine inhibited the Ca2+ stimulated enzyme in a dose dependent manner (ID50 = 50 microM) but had no effect on the basal phosphodiesterase activity.
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PMID:Function of calmodulin in mammalian sperm: presence of a calmodulin-dependent cyclic nucleotide phosphodiesterase associated with demembranated rat caudal epididymal sperm. 632 56

Rabbit sperm pyruvate kinase remains bound to the cell structure of hypotonically treated mature rabbit epididymal spermatozoa (HTRES). It displays kinetic behavior very similar to that of rabbit muscle pyruvate kinase with regard to KM values for substrates, activation by monovalent and divalent cations, inhibition by phenylalanine which is reversed by alanine, and lack of activation by fructose-1,6-biphosphate. The flagellar ATPase also remains bound to the cell structure of HTRES, whose motility may be reactivated by a source of ATP. It requires Mg+2 for activity; the KM for both ATP and MG+2 is 0.2 mM, implying that MgATP is the substrate. The ATPase activity is not inhibited by ouabain, oligomycin, or vanadate, which also do not affect reconstituted motility, and is not affected by cyclic AMP in the presence of an inhibitor of phosphodiesterase. The activities of pyruvate kinase and the flagellar ATPase in a given preparation of HTRES are comparable. Rabbit spermatozoa have a metabolic strategy which is very similar to muscle cells. This suggests that the major use of the sperm cell's metabolic machinery is maintenance of energy for the contractile work of motility and that only minor amounts of metabolic energy appear to be consumed in other reactions, including those involved in fertilization.
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PMID:Properties of pyruvate kinase and flagellar ATPase in rabbit spermatozoa: relation to metabolic strategy of the sperm cell. 644 94

Sperm surface changes during in vitro capacitation were examined with the help of an assay system using lectin-coated agarose beads. The nature and intensity of binding of epididymal spermatozoa to beads depended entirely on the particular stage of capacitation and the type of lectin attached to the bead surface. Fresh epididymal spermatozoa bound readily to beads coated with Con A, LCA, WGA, and PNA, but not with seven other lectins. During capacitation there was a constant decline in sperm binding to beads, and spermatozoa cultured for 4-5 hr bound only to those coated with Con A. A dramatic increase in sperm binding to Con A-coated agarose beads occurred between 4.5 and 5 hr, when large numbers of hyperactivated spermatozoa adhered, predominantly through their flagellae, to form large clumps on the beads. The clumping of spermatozoa on Con A-coated beads was enhanced in the presence of stimulators of capacitation (i.e., taurine, hypotaurine, and phosphodiesterase inhibitors) and was suppressed in the presence of various metabolic inhibitors (i.e., sodium azide and local anesthetics). The implications of these results are that the carbohydrate components of the entire surface of spermatozoa undergo striking changes during capacitation, and a close relationship may exist between the sperm surface and the metabolic changes occurring within capacitating spermatozoa. Sperm-bead binding assays are clearly able to recognize surface changes in asynchronous populations of motile spermatozoa and, due to their simplicity and speed, should prove to be valuable in gaining a greater understanding of the biochemistry of sperm capacitation.
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PMID:Lectin-coated agarose beads in the investigation of sperm capacitation in the hamster. 673 31

The activity of adipose tissue hormone-sensitive lipase in animals with hyperinsulinemia has been reported to be increased compared with that in control animals. We examined whether this results from a direct effect of insulin on the tissue and whether it is accompanied by alteration in the regulation of lipolysis. When rat epididymal fat pads are incubated in culture medium with bovine serum albumin for 2-4 h with 2 ng/ml or 50 microU/ml of insulin, hormone-sensitive lipase activity in the postmicrosomal supernatant fraction after acid precipitation and activation with ATP-Mg2+ increases significantly compared with preparations from tissues incubated with the vehicle. The specific activities of hormone-sensitive lipase in sonicates of adipocytes after primary culture with insulin at concentrations from 10 to 4000 ng/ml (250 microU to 100 mU/ml) increase in an insulin-dose-related manner. Lipolysis in response to 10(-7) M isoproterenol also increases in an insulin-dose-dependent manner. Enhancement of isoproterenol-mediated lipolysis is not attributable to a difference in the triglyceride content of the cells. Lipolysis caused by the beta-agonist could be completely blocked by the simultaneous presence of insulin in both control and insulin-treated cells reflecting normal responsiveness of both types of cells to the acute effect of insulin. Although an increase in lipolysis is seen with norepinephrine and growth hormone after insulin treatment, other lipolytic agents such as ACTH, thyrotropin, and glucagon evoke similar responses in insulin-treated and control cells. The simultaneous presence of growth hormone and insulin during the 16-h culture results in additive effects on the subsequent response of the cells to 10(-7) M isoproterenol compared with the responses of the cells cultured with each hormone alone. beta-Agonist-mediated cAMP accumulation in the presence of Ro-20.1724, a specific phosphodiesterase inhibitor, is significantly higher in cells cultured in the presence of insulin than in control cells. Forskolin (1-25 microM) increases the lipolytic responses of insulin-treated cells compared with control cells, but the maximal response of the insulin-treated cells to forskolin is lower than that to isoproterenol. We conclude that changes produced by chronic insulin treatment involve more than one site along the lipolytic cascade.
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PMID:Chronic exposure of rat fat cells to insulin enhances lipolysis and activation of partially purified hormone-sensitive lipase. 839 27


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