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)

ICI 66082, a cardioselective beta-adrenoceptor blocking agent, was found to produce hypoglycaemia in fasted rats. In fed rats a hyperglycaemic response was observed. The drug produced hypoglycaemia in fed adrenalectomised animals. The hypoglycaemic response to ICI 66082 was accompanied by elevations in plasma immunoreactive insulin (IRI) concentrations. The drug also reduced plasma glucose and increased IRI in moderately alloxan-diabetic rats. In severely diabetic animals The drug did not increase IRI concentrations and did not unequivocally lower plasma glucose concentrations. In vitro experiments showed ICI 66082 to increase glucose uptake by rat diaphragm muscle and epididymal adipose tissue. the hypoglycaemic response may be mediated by increases in plasms IRI concentrations with a possible contribution from direct effects of the drug on peripheral glucose utilization. As these responses differ from those published in relation to other beta-adrenoceptor blocking drugs it is unlikely that the effects are due to beta-adrenoceptor blockade. However, like other beta-adrenoceptor blocking drugs ICI 66082 reduced isoprenaline-mediated increase in plasma IRI.
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PMID:Effect of ICI 66082, a beta-adrenoceptor blocking drug on blood glucose in the rat. 80 52

The potent anabolic effects of the beta 2-adrenoceptor agonist clenbuterol on skeletal muscle have been reported to be independent of actions on beta-adrenoceptors. In the present study clenbuterol, presented to rats in the diet (4 mg/kg), caused significant increases in gastrocnemius muscle mass, protein, and RNA content and a decrease in epididymal fat pad mass. These effects were not mimicked by oral administration of the beta 2-adrenoceptor agonist salbutamol even at high dose (52 mg/kg diet), and the effects of clenbuterol were not inhibited by addition of DL-propranolol (200 mg/kg diet). However, the selective beta 2-antagonist ICI-118,551 (200 mg/kg diet) reversed the anabolic effects of clenbuterol, and a high dose of DL-propranolol (1,000 mg/kg diet) also inhibited these actions of clenbuterol. Furthermore, continuous infusion of salbutamol (1.15 mg.kg body wt-1.day-1) via miniosmotic pumps did cause significant increases in muscle mass, protein, and RNA content. These results indicate that the anabolic effects of clenbuterol are dependent on interaction with the beta 2-adrenoceptor. However, a long duration of action appears to be required to induce the anabolic effects of beta 2-agonists.
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PMID:Anabolic effects of clenbuterol on skeletal muscle are mediated by beta 2-adrenoceptor activation. 132 47

A protocol for the rapid purification of the glycerol dehydrogenase (glycerol: NAD+ 2-oxidoreductase, EC 1.1.1.6) from the thermophile Bacillus stearothermophilus has been developed using a combination of chromatographic techniques including affinity chromatography on a Sepharose-immobilised triazine dye (Procion red, HE3B, ICI). Substrate specificity has been examined and Km values determined. The protein has been shown to have an oligomeric Mr of approx. 180,000 and consists of four identical subunits of Mr 42,000. Exposure to chelating agents (e.g., EDTA) leads to total loss of activity; the EDTA-inactivated enzyme can be reactivated by Zn2+ and requires 1 mol equivalent of zinc per subunit for full catalytic activity. Other divalent cations such as Cd2+ and Co2+ will reactivate the apo-enzyme but yields an enzyme of lower specific activity. The enzyme binds 1 equivalent of NADH per subunit and during catalysis transfers the 4-pro-R hydride from the nicotinamide ring of the reduced-coenzyme to the substrate. Glycerol increases the dissociation constant for the interaction between NADH and Zn-metallo-glycerol dehydrogenase (ZnGDH) but has no effect on the equilibrium between NADH and metal-depleted enzyme.
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PMID:Isolation and characterisation of the glycerol dehydrogenase from Bacillus stearothermophilus. 249 67

A sustained-release formulation of a potent gonadotropin-releasing hormone (GnRH) agonist, Zoladex (D-Ser(But),6 Aza Gly10-GnRH; ICI 118,630; goserelin), was administered subcutaneously (3.6 mg/depot) to male rats once every 28 days for 2-24 wk to determine the extent to which pituitary-testis function could be suppressed and whether suppression was maintained throughout the period of treatment. Administration of Zoladex resulted in sustained decreases in weight of the testis, epididymis, seminal vesicles and prostate gland. The decreases were apparent within 2 wk of initiating treatment. Patchy degeneration of the seminiferous tubules and atrophy of the Leydig cells were observed, but did not progress beyond the degree observed after 1 month of treatment. Serum and testis testosterone were markedly depressed after 2 wk of treatment, as was testis [125I]hCG binding. Serum gonadotropins were also reduced by treatment. Serum androgen binding protein (ABP) was elevated, testis ABP content remained unchanged, and epididymal ABP content was reduced. The changes are consistent with the hypothesis that this compound affects both the anterior pituitary gland and the testis. These findings indicate that depot delivery systems are a convenient way to administer GnRH analogs for sustained treatment schedules.
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PMID:Prolonged suppression of rat testis function by a depot formulation of Zoladex, a GnRH agonist. 253 93

1. The nature of the rat epididymal adipocyte beta-adrenoceptor was investigated by studying the effects of beta 1- and beta 2-selective antagonists on lipolysis induced by (-)-isoprenaline and the lipolytically selective agonist BRL 37344. 2. From 10 nM to 10 microM, the potent and highly selective beta 1-adrenoceptor antagonist CGP 20712A did not influence the concentration-response curve (CRC) of BRL 37344 whereas small but consistent shifts to the right of the (-)-isoprenaline-induced CRC were observed. Clear rightward shifts of the CRCs induced by both (-)-isoprenaline and BRL 37344 were produced only at 100 microM CGP 20712A with the corresponding pA2 values being 4.80 and 4.61, respectively. 3. When the beta 2-selective antagonist ICI 118,551 was used at 10 microM and higher, clear and concentration-dependent shifts to the right of the CRCs of both agonists were observed. The slopes of the Schild plots did not deviate significantly from unity, the pA2 values being 5.49 and 5.33 against (-)-isoprenaline and BRL 37344, respectively. 4. The results demonstrate that (-)-isoprenaline-induced lipolysis in rat white adipocytes is mediated predominantly by atypical beta-adrenoceptors, whereas the typical beta 1-adrenoceptors play a small, subordinate role. The lipolytically selective agonist BRL 37344 acts solely through atypical beta-adrenoceptors.
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PMID:Direct evidence for the atypical nature of functional beta-adrenoceptors in rat adipocytes. 257 16

We report a sex- and depot-specific response of rat adipose tissues to gonadal steroids. The epididymal fat pad in male rats responded to androgens (testosterone and dihydrotestosterone; DHT), but not to 17beta-estradiol (E2), by increased specific activity of the brain type isozyme of creatine kinase (CK). In female rats, the parametrial fat as well as the fat surrounding the spleen responded to E2 but not to dihydrotestosterone. In both sexes, subcutaneous fat from the inguinal, abdominal or thigh region did not respond to any sex steroid. The parametrial fat showed increasing responsiveness to E2 during postnatal development, in parallel to the response of the uterus. In cycling female rats, parametrial fat showed the highest basal activity of CK at estrus; stimulation by E2 was achieved on all the other days of the cycle. Both phytoestrogens and diethylstilbestrol stimulated CK activity in both parametrial and spleen fat, in parallel to their estrogenic potencies; parametrial fat also responded to progesterone. The stimulation of CK activity in parametrial fat by E2 was completely blocked by actinomycin D or cycloheximide. Treatment with the antiestrogen, tamoxifen, caused moderate stimulation of CK activity in parametrial fat as well as partial inhibition of E2 stimulation of CK activity; the "pure" antiestrogen ICI 164,384 had no agonistic effect and completely blocked the E2 effect. Ovariectomy caused an increased response to E2 without changes in the basal CK activity, but did not lead to any response to DHT. As well as being a reliable response marker, the differential modulation of CK activity can thus serve to distinguish adipose cells from different sources.
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PMID:Sex and depot-specific stimulation of creatine kinase B in rat adipose tissues by gonadal steroids. 936 2

We have demonstrated previously that rat adipose tissue showed sex and depot-specific responses to gonadal steroids. The epididymal fat pad in males responded exclusively to androgens by increased specific activity of the brain type isozyme of creatine kinase (CK). In females, the parametrial adipose tissue responded exclusively to estrogens. The present study was undertaken to follow the responsiveness to steroid hormones, and the presence of estrogen receptors (ER), in 3T3L1 cells during their differentiation from pre-adipocytes to adipocytes. In pre-adipocytes in which the basal CK specific activity is low, there was no CK response to 17beta estradiol (E2) or dihydrotestosterone (DHT). Differentiation of the cells into adipocytes was accompanied by increased basal CK activity which was stimulated by E2, but not by DHT. Responsiveness to E2 began 5 days after switching pre-adipocytes to differentiation medium. Upon differentiation, ER became demonstrable in the cell nuclei by staining with FITC labeled anti-idiotypic antibody (clone 1D5) directed against the steroid binding domain of ER. The response to E2 was time-dependent and blocked completely by cycloheximide or actinomycin D. 1D5 itself, which has an estrogen mimetic effect, stimulated CK activity in the cells similarly to E2. The antiestrogen tamoxifen which also stimulated CK activity in the adipocytes, completely blocked E2 action. The 'pure' antagonist of E2, ICI 164,384 and the tissue-selective antiestrogens, raloxifene or tamoxifen methiodide were also complete antagonists with no agonistic effects. The response of the 3T3L1 adipocytes to E2 was upregulated by 1,25(OH)2D3. Moreover, IGF1 was also a potent stimulator of CK in these cells, and therefore may mediate partially the stimulation by E2. Transient transfection of the pre-adipocytes with ER permitted E2 induction of CK. Thus, the appearance of ER and concomitant responsiveness to E2 is another hormone-related change occurring in 3T3L1 cells during differentiation, in addition to changes such as development of insulin responsiveness. The interactions in this system provide a useful in vitro model for investigating the development of responsiveness to E2.
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PMID:Estrogen stimulation of creatine kinase B specific activity in 3T3L1 adipocytes after their differentiation in culture: dependence on estrogen receptor. 944 43

1. gamma-Glutamyl-transpeptidase (gamma-GTP), present at low levels in the testis, seminal vesicle, prostate gland and epididymis in rat at 4 days of age, showed rapid developmental increases at the time of weaning. 2. Administration of nonylphenols (NP) to the neonatal male rat pup (from days 1 to 15) impaired the subsequent development of gamma-GTP in the epididymis but not in the testis, seminal vesicles or prostate gland. 3. Single injection of NP to weaned pups at approximately 22 days of age decreased gamma-GTP in the epididymis but not in other male accessory sex organs. This effect was transient, dose-dependent and blocked by the oestrogen receptor-specific antagonist ICI 182,780. 4. Single injection of oestradiol to weaned rat at approximately 22 days of age also decreased gamma-GTP in the epididymis but not in the testis, prostate gland or seminal vesicles. 5. In in vitro assays, NP did not inhibit epididymal gamma-GTP activity even at 100 microM final concentration. Under similar conditions, acivicin, a specific inhibitor for gamma-GTP, showed a dose-dependent inhibition of gamma-GTP activity. 6. It is suggested that NP impair gamma-GTP expression in the epididymis of developing male rat and act in part via the oestrogen receptor.
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PMID:Modulation of rat epididymal gamma-glutamyl transpeptidase by nonylphenols. 1103 10

In vitro lipolysis stimulated by low (-)-isoprenaline concentrations (< or =30 nM) in epididymal white adipocytes from Sprague-Dawley rats was inhibited at least 60-80% by the specific beta1-antagonists LK 204-545 and CGP 20712A (1 microM), suggesting that at these low (10 nM) concentrations of (-)-isoprenaline lipolysis was primarily (80%) but not solely mediated via beta1-adrenergic receptors. Low concentrations (100 nM) of (-)-noradrenaline and formoterol also confirmed a role for beta1-adrenergic receptors in mediating lipolysis at low concentrations of these agonists. At higher agonist concentrations, beta3-adrenergic receptors were fully activated and were the dominant beta-adrenergic receptor subtype mediating the maximum lipolytic response, and the maximum response was not affected by the beta1-antagonists, demonstrating that the beta3-receptor is capable of inducing maximum lipolysis on its own. Studies of lipolysis induced by the relatively beta2-selective agonist formoterol in the presence of beta1-blockade (1 microM CGP 20712A) demonstrated the inability of the beta2-selective antagonist ICI 118-551 to inhibit the residual lipolysis at concentrations of ICI 118-551 < or = 1 microM. Higher concentrations of ICI 118-551 inhibited the residual formoterol-induced lipolysis competetively, but with low affinity (approximately 500-fold lower than its beta2-adrenergic receptor pA2, 7.80 +/- 0.21), suggesting that formoterol was not acting via beta2-adrenergic receptors. These data are consistent with beta1-adrenergic receptors playing an important role in lipolysis at physiological but not pharmacological concentrations of catecholamines and that beta2-adrenergic receptors play no obvious direct role in mediating beta-adrenergic receptor agonist-induced lipolysis in vitro. Finally, racemic-SR 59230A, unlike the pure (S, S)-isomer (a beta3-selective antagonist), was found to be a nonselective antagonist at the three beta-adrenergic receptor subtypes, showing that the other enantiomers have different selectivity.
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PMID:Role of beta-adrenergic receptor subtypes in lipolysis. 1130 Mar 57

A role for oestrogen in regulating fluid reabsorption in the monkey epididymis was recently demonstrated. Here, these studies are extended to identify potential oestrogen-regulated proteins in the cauda region of monkey epididymis treated with vehicle and oestrogen receptor antagonist (ICI 182780). Two-dimensional electrophoretic analysis was used to identify the proteins. The results indicated down-regulation of WNT4 in the ICI-182780-treated monkey cauda. In addition, the Wnt4 mRNA concentration was also reduced in the caput regions of ICI-182780- treated rats and oestrogen receptor knockout mice. WNT4 is a key regulator of gonadal differentiation in humans and mice and plays a pivotal role in early mouse embryogenesis. The results of the present study establish the presence of WNT4 in the monkey epididymis and its regulation by oestrogen, and suggest a role for WNT4 in maintaining epididymal homeostasis.
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PMID:Oestrogenic regulation and differential expression of WNT4 in the bonnet monkey and rodent epididymis. 1940 Sep 99


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