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)

In this study the role of cyclic AMP in the antilpolytic effect of the alpha-adrenergic agents methoxamine and phenylephrine in hamster epididymal adipocytes was studied. Both methozamine and phenylephrine lowered the very high levels of cyclic AMP that were produced by high concentrations of isoproterenol (10 muM) or ACTH (100 MU/ml), and partially inhibited lipolysis. When lower concentrations of isoproterenol were used, the antilipolytic effect of phenylephrine and methoxamine was still evident. Under these conditions methoxamine produced a slight suppression of cyclic AMP levels while phenylephrine increased accumulation of cyclic AMP. It follows, therefore, that the inhibition of lipolysis by the alpha agents is most likely unrelated to changes in cyclic AMP levels; in contrast, phenylephrine promoted lipolysis and increased cyclic AMP levels. When the stimulus for lipolysis was provided by methylxanthines a different picture emerged. Methoxamine antagonized lipolysis and lowered cyclic AMP levels. In the presence of propranolol, phenylephrine lowered cyclic AMP levels and suppressed methylxanthine-accelerated lipolysis. It is suggested that when methy xanthines provide the stimulus for lipolysis the antilipolytic effect of methoxamine and phenylephrine (in the presence of propranolol) may be mediated by the suppression in cyclic AMP levels.
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PMID:Inhibition of lipolysis in hamster epididymal adipocytes by selective alpha-adrenergic agents. Evidence for cyclic AMP-dependent and independent mechanisms. 9 May 27

Isolated fat cells from rat epididymal adipose tissue were incubated with various lipolytic hormones in the absence and presence of the alpha-adrenergic blocking agent phentolamine. Lipolysis, stimulated by noradrenaline, isoproterenol, or ACTH, was inhibited dose-dependently by phentolamine. At concentrations of phentolamine where lipolysis was already inhibited, phentolamine had a biphasic effect on hormone-stimulated formation of cAMP. Low concentrations of phentolamine enhanced cAMP formation, while high concentrations inhibited cAMP. The additional increase of cAMP formation by phentolamine was only seen with maximally effective concentrations of noradrenaline, isoproterenol, and ACTH. Half-maximally effective concentrations were invariably inhibited by phentolamine. The activity of noradrenaline-stimulated adenylate cyclase of fat-cell plasma membranes was inhibited by phentolamine, whereas cAMP phosphodiesterase activity was unaffected.
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PMID:Biphasic effect of the alpha-adrenolytic phentolamine on hormone-stimulated formation of cyclic adenosine-3',5'-monophosphate in isolated fat cells of rats. 16 51

The possibility has been explored that decreases of adenylate cyclase may explain diminished hormone sensitivity of adipose tissue with aging. Isolated cells were prepared from epididymal fat pads of rats 1-, 2-, 6-, 12-, and 24-mo old, fixed in OSO4, and sized and counted with a Coulter apparatus. Adenylate cyclase was assayed in cell membranes (ghosts) using [alpha-32P] ATP as substrate and expressed as cyclic [32P] AMP/10 min per mg protein or per 10(6) cells. Enzyme activity was determined for the basal state and in the presence of varying concentrations of glucagon, ACTH, epinephrine, and fluoride. Basal activity per cell increased in threefold between 1 and 2 mo with a comparable increase in cell surface area, suggesting synthesis of enzyme along with new cell membrane. Although epinephrine stimulated adenylate cyclase 8-fold and fluoride 12-fold throughout the life-span of the rat, stimulated activity paralleled basal levels, decreasing 60% between 2 and 24 mo per mg protein and 40% between 6 and 24 mo per cell. Glucagon stimulated adenylate cyclase 4.5-fold relative to basal in the 1-mo-old rat, but its effect then rapidly decreased and was absent by 12 mo. The fourfold stimulation by ACTH noted in the 1-mo-old animals decreased gradually with age but was still twice basal at 24 mo. Since no significant change of cell size occurred after 6 mo, diminished hormone sensitivity with senescence cannot be related to cell size. Similar age-related patterns of hormonal activation were evoked by 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], a nucleotide analogue which increased both basal- and hormone-activated enzyme at all ages studied. Dose-response curves to hormones, fluoride, and GMP-P (NH)P were not affected by age. High Mg++ (50 mM) in the presence of GMP-P-(NH)P stimulated adenylate cyclase to levels greater than with fluoride, but a similar loss of activity with aging was still observed. Loss of hormone receptors may partially explain the age-related decreases of glucagon and ACTH-sensitive adenylate cyclase, but decreased basal-, epinephrine-, fluoride-, and GMP-P-(NH) P-stimulated responses suggest loss of the catalytic component of the adenylate cyclase enzyme complex in the aging fat cell membranes.
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PMID:Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging. 17 40

Clomiphene (10(-3) - 10(-2) M) in a dose-dependent manner inhibited the lypolytic response of isolated rat epididymal adipose tissue and fat cells to epinephrine, ACTH, and dibutyryl-cyclic AMP. Furthermore, it reduced the non-hormonally stimulated activity of a crude preparation of lipase from epididymal adipose tissue. The accumulation of cyclic AMP produced by epinephrine in fat cells was not prevented by clomiphene at a concentration causing antilipolytic activity. It is concluded from these results that clomiphene unlike most other antilipolytic drugs exerts its antilipolytic effect by an inhibition of the lipase rather than by inhibition of adenylcyclase.
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PMID:Evaluation of the antilipolytic action of clomiphene in vitro. 17 45

Starvation did not cause increase of hormone-sensitive lipase in rat epididymal adipose tissue. Adrenaline did not activate lipase in the fat cells, although it accelerated the release of free fatty acids from the cells. The results suggest that the mechanism of the stimulation of lipolysis by adrenaline is different from that in the cyclic AMP theory. Adrenaline-sensitive fat globules were prepared by hypotonic treatment of fat cells. Lipolysis in the fat globules was stimulated by adrenaline. It was shown that adrenaline-induced lipolysis in the fat globules was not due to activation of lipase but to initiation of a reaction between lipase and triglyceride. It is well known that calcium ions are essential for ACTH-induced lipolysis and that the hormone stimulates calcium uptake into adipose tissue. It was demonstrated that calcium ions accelerated formation of a complex between fat and lipase. The mechanism of the actions of adrenaline and ACTH are discussed on the basis of these results.
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PMID:Mechanism of actions of adrenaline and ACTH in fat mobilization. 17 4

2 acidophilic and 3 basophilic cell types were identified in the pars distalis of the soft-shelled turtle (Trionyx sinensis) and their function was interpreted. Comparison of seasonal fluctuations in cytoplasmic granulation and cell and nuclear size with seasonal patterns of gonadal, adrenal, and thyroid activities indicated specific functions for each of the cell types. The activity of basophils 1 closely paralleled the seasonal pattern of the thyroid cycle, while basophils 2 are most likely follicle-stimulating-hormone-secreting gonadotropes whose activity correlated with the seasonal pattern of spermatogenesis in the seminiferous tubules. The secretory pattern of the basophils 3 was correlated with the functional activity of the testicular interstitial cells, which suggests that these are luteinizing-hormone-secreting cells. This is supported by a high degree of androgen secretion during the epididymal cycle which coincided with rapid degranulation of these cells at a time when spermatogenesis was in arrest. No apparent correlation between adrenal activity and the basophils 3 cycle was observed. It is suggested that the chromophobic cells may be the site of ACTH secretion. Acidophils 1 increased their activity in the autumn and are probably lactotropic in function, while acidophils 2 activity was stable throughout the year, which suggests that they are likely to be somatotropes.
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PMID:Adenohypophysial cell-types in the pituitary gland of the soft-shelled turtle, Trionyx sinensis. I. Seasonal cycles. 18 89

In this work the kinetics of activation of the cyclic AMP-dependent protein kinase by several catecholamines and ACTH, have been studied in rat epididymal fat pads and isolated fat cells. The method of Soderling and co-workers which permits the measurement of the state of activation of the protein kinase after hormonal stimulation in adipose tissue, has been used. Kinetics experiments where norepinephrine was used showed that the results obtained with isolated cells conform to the models of Sutherland and Brostrom and co-workers. Wtih intact tissue, norepinephrine not only stimulates the protein kinase activity measured without exogenous cyclic AMP but also the total activity measured in the presence of cyclic AMP (5 X 10(-6) M); thus the effect of norepinephrine, obtained during incubation of the tissue, and that of cyclic AMP, added to the soluble fraction after incubation, were additive. This effect seems to be of the beta type because it is blocked completely by propranolol. A weak, additive but significant effect was also obtained with epinephrine and isoproterenol but not with ACTH. Neither cyclic GMP nor cyclic IMP seems implicated in this effect. It was shown that stroma vascular cells which are present in the fat pads are not involved. These results suggest that the effects of norepinephrine on the protein kinase of the fat pads cannot be completely explained by the model of Brostrom and colleagues.
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PMID:Additive effects of norepinephrine and cyclic AMP on the activation of the protein kinase from adipose tissue. 18 9

Glycerol release from epididymal fat fragments of young adult (3-month old) ob/ob mice was three times lower than normal, on a tissue weight basis. Dose-response curves in response to isoproterenol and ACTH-(1--24) indicated that the capacity of the lipolytic process was reduced. However, the sensitivity to both hormones was normal, i.e. greater for ACTH than for isoproterenol. The burst of cyclic AMP observed at 7 minutes was affected even more than the lipolytic capacity in adipose tissue from obese mice. This was already observed in 1-month old animals, i.e. at a time when total body weight was still normal. It is concluded that the adenylate cyclase system is defective in adipose tissue of ob/ob mice. Besides, glucagon, vasoactive intestinal polypeptide, and secretin failed to stimulate glycerol release and cyclic AMP accumulation in both ob/ob, ob+/ob+, and HA-ICR mice, suggesting that mouse adipose tissue does not possess receptors for this group of hormones.
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PMID:Lipolysis and cyclic AMP levels in epididymal adipose tissue of obese-hyperglycaemic mice. 20 30

The present study reports the effects on lipolysis occurring in isolated rat epididymal adipocytes of several agents which have each been found to interfere with membrane calcium transport in a variety of tissues. As reported by other workers, the local tetracaine was a strong inhibitor of hormone accelerated but not of basal lipolysis. The bivalent cations Mn2+ and Co2+ were similarly found to inhibit lipolysis stimulated with either epinephrine, ACTH, theophylline or dibutyryl cyclic AMP, whereas basal lipolysis was not markedly altered. This effect of Mn2+ and Co2+ was not mimicked by either Sr2+, Ba2+, Mg2+ or Ca2+. Cyclic AMP levels in adipocytes stimulated with epinephrine or ACTH tended to be higher in the presence of Mn2+ and Co2+. It is concluded, therefore, that Mn2+ and Co2+ inhibit lipolysis by uncoupling cyclic AMP accumulation from activation of triglyceride lipase. In contrast to Mn2+ and Co2+, the calcium antagonists La3+ and D600 were without effect on lipolysis. The antilipolytic effect of tetracaine, Mn2+ and Co2+ was found to persist in the absence of extracellular calcium, suggesting therefore that the antilipolytic effect of these drugs is unrelated to inhibition of calcium influx into adipocytes. The possibility is discussed that lipolytic agents cause an intracellular redistribution of calcium ion and that local anesthetics, Mn2+ and Co2+ interfere with lipolysis by preventing this intracellular redistribution of calcium.
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PMID:Calcium antagonists and lipolysis in isolated rat epididymal adipocytes: effects of tetracaine, manganese, cobaltous and lanthanum ions and D600. 20 97

The plasma level of free fatty acids (FFA) in adrenalectomized rats increases by 50% after treatment with aldosterone (2 microng/100 g rat). Lipolytic activity in peripheral fat tissue is lowered after adrenalectomy and doubles after in vivo administration of aldosterone to adrenalectomized rats (measured as free fatty acid release in vitro from epididymal fat tissue). Lypolysis of adipose tissue stimulated by the in vitro presence of ACTH also increases after in vivo administration of aldosterone. Incorporation of intravenously administered label from U-14C-palmitate into total extractable lipid of renal tissue is augmented 3 h after aldosterone administration to adrenalectomized rats, while no increase of the radioactivity is observed in total lipid from liver tissue. Treatment with aldosterone does not affect the total lipid content of kidney or liver in adrenalectomized rats. The oxygen consumption rate of kidney cortex slices with lactate, beta-hydroxybuterate or acetoacetate as substrates is lowered after in vivo administration of aldosterone to adrenalectomized rats. With slccinate, however, the respiratory rate of kidney slices increases after aldosterone treatment of adrenalectomized rats, the ouabain-sensitive respiration being more affected than the ouabain-insensitive respiration. An interpretation of the O2 consumption data implicating competition of lipid metabolism for CoA-SH is discussed.
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PMID:Effects of aldosterone on lipid metabolism and renal oxygen consumption in the rat. 55 89


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