摘要:

Abstract:Melatonin is a very potent and efficient endogenous radical scavenger. The pineal indolamine reacts with the highly toxic hydroxyl radical and provides on‐site protection against oxidative damage to biomolecules within every cellular compartment. Melatonin acts as a primary non‐enzymatic antioxidative defense against the devastating actions of the extremely reactive hydroxyl radical. Melatonin and structurally related tryptophan metabolites are evolutionary conservative molecules principally involved in the prevention of oxidative stress in organisms as different as algae and rats. The rate of aging and the time of onset of age‐related diseases in rodents can be retarded by the administration of melatonin or treatments that preserve the endogenous rhythm of melatonin formation. The release of excitatory amino acids such as glutamate enhances endogenous hydroxyl radical formation. The activation of central excitatory amino acid receptors suppress melatonin synthesis and is therefore accompanied by a reduced detoxification rate of hydroxyl radicals. Aged animals and humans are melatonin‐deficient and more sensitive to oxidative stress. Experiments investigating the effects of endogenous excitatory amino acid antagonists and stimulants of melatonin biosynthesis such as magnesium may finally lead to novel therapeutic approaches for the prevention of degeneration and dysdifferentiation associated with diseases related to prematur

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1993.tb00498.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:2‐[125]Iodomelatonin binding sites in membrane preparations of pigeon spleen have been characterized. The binding was stable, saturable, reversible, and of high affinity. Rosenthal and Hill analyses showed that the radioligand‐receptor interaction involved a single class of binding sites. Analysis of the binding results of spleens collected during mid‐light revealed an equilibrium dissociation constant (Kd) of 36.6 ± 4.8 pmol/1 (mean ± sem, n = 10) and a maximum density (Bmax) of 2.3 ± 0.2 fmol/mg protein. There was no significant difference in the Kd (46.9 ± 5.0 pmol/1) or the Bmax values (2.4 ± 0.3 fmol/mg protein) for spleens collected during mid‐dark (n = 9), although the mid‐dark serum and pineal melatonin levels were significantly higher (P<0.05) than the corresponding mid‐light values. Kinetic analysis showed a Kd of 8.6 ± 2.0 pmol/1 (n ± 4), in agreement with that derived from the saturation studies. Except for inhibition by 2‐iodomelatonin, melatonin, 6‐chloromelatonin, 6‐hydroxymelatonin and N‐acetylserotonin, the other indoles or neurotransmitters tested have little inhibition on the binding. In addition, guanosine 5′‐O‐(3‐thiophosphate) (GTPγS), a nonhydrolysable analog of GTP, was found to inhibit the binding in a dose‐dependent manner. Saturation studies revealed that this is due to a decrease in both the affinity and density of the binding sites. These data suggest that a single type of melatonin receptor is found in the pigeon spleen and that the site is coupled to a guinine nucleotide binding protein (G‐protein). Our findings support a direct pinea

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1993.tb00499.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The possible diurnal variation in cardiac [Ca2++ Mg2+]‐dependent ATPase (Ca2+pump) activity and the influence of pinealectomy and melatonin on this enzyme in rat heart have been studied. Lowest levels of cardiac sarcolemma] membrane [Ca2++ Mg2+]‐dependent ATPase activity were measured in late afternoon in rats kept under a 14:10 light:dark cycle. Late in the dark phase the enzyme activity began to increase with the rise continuing until 0900, 3 hr after light onset. These time‐dependent changes in [Ca2++ Mg2+]‐dependent ATPase activity did not occur in either pinealectomized or light‐exposed rats suggesting that melatonin, secreted from the pineal gland during the night, induces the change in [Ca2++ Mg2+]‐dependent ATPase activity. In vitro studies in which cardiac tissue was incubated in the presence of melatonin over a wide range of doses showed that this indole stimulated the Ca2+pump. The half‐maximal effect of melatonin was observed at a melatonin concentration of 28 ng/ml. These findings suggest that the daily change in [Ca2++ Mg2+]‐dependent ATPase activity in the sarcolemma of heart tissue is a result of the circadian rhythm in pineal melatonin production and secretion. These findings may be applicable to normal car

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1993.tb00500.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Melatonin, an indolamine synthesized in the pineal gland, is known to have antiprostanoid activity. The inhibition of platelet aggregation induced by melatonin has been proposed to take place through the cyclooxygenase pathway. In the present study, we found that melatonin has a marked inhibitory effect on collagen, arachidonic acid (AA), adenosine diphosphate (ADP), epinephrine, and A23187‐induced aggregation in platelet‐rich plasma. On the other hand, using metrizamide‐filtered platelets resuspended in Tyrode's buffer, melatonin fails to suppress AA‐induced platelet aggregation and14C‐5‐HT release. Under the same conditions, melatonin inhibits collagen‐induced platelet activation; however, the addition of threshold doses of AA (0.3 mM) abrogates this effect. These studies suggest that melatonin also inhibits platelet function at a stage preceding the cyclooxygenase‐de

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1993.tb00501.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Plasma melatonin concentrations were measured in Japanese quail held under different photoperiods and constant darkness (3 hr under T = 27 hr cycles (LD 3:24) compared with T = 24 hr cycles (LD 3:21). This property is consistent with the melatonin oscillator being

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1993.tb00502.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY