Inhibition of cerebellar nitric oxide synthase and cyclic GMP production by melatonin via complex formation with calmodulin

Pozo, David; Reíter, Russel J.; Calvo, Juan R.; Guerrero, Juan M.

doi:10.1002/(sici)1097-4644(19970601)65:3<430::aid-jcb12>3.0.co;2-j

Cited by 271 publications

(203 citation statements)

References 39 publications

(34 reference statements)

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“…Melatonin also inhibits the activity of the enzyme nitric oxide synthase (NOS) [94][95][96], which catalyzes the formation of NO•. In inflamed tissues, NO released after cytokine stimulation contributes to the development of micro-vessel damage and vascular hyporeactivity [97].…”

Section: Effects Of Melatonin On the Arachidonic Acid Metabolismmentioning

confidence: 99%

Melatonin: A pleiotropic molecule regulating inflammation

Radogna

Diederich

Ghibelli

2010

Biochemical Pharmacology

301

244

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Melatonin is a neurohormone produced by the pineal gland that regulates sleep and circadian functions. Melatonin also regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses. Melatonin demonstrates endocrine, but also paracrine and autocrine effects in the leukocyte compartment: on one side, leukocytes respond to melatonin in a circadian fashion; on the other side, leukocytes are able to synthesize melatonin by themselves.With its endocrine and paracrine effects, melatonin differentially modulates pro-inflammatory enzymes, controls production of inflammatory mediators such as cytokines and leukotrienes and regulates the lifespan of leukocytes by interfering with apoptotic processes. Moreover, its potent anti-oxidant ability allows scavenging of oxidative stress in the inflamed tissues. The interesting timing of pro-and anti-inflammatory effects, such as those affecting lipoxygenase activity, suggests that melatonin might promote early phases of inflammation on one hand and contribute to its attenuation on the other hand, in order to avoid complications of chronic inflammation. This review aims at giving a comprehensive overview of the various inflammatory pathways regulated by this pleiotropic hormone.

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Section: Effects Of Melatonin On the Arachidonic Acid Metabolismmentioning

confidence: 99%

Melatonin: A pleiotropic molecule regulating inflammation

Radogna

Diederich

Ghibelli

2010

Biochemical Pharmacology

301

244

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“…16 It en han ces abi lity of cells to re sist oxi da ti ve da ma ge by in hi bi ting the pro-oxidant nit ric oxi de syntha se. 17 An ti o xi dant ca pa city of me la to nin on plas ma has be en well es tab lis hed in the li te ra tu re. 9 Hus se in et al 18 sho wed that a sing le and high do se of me la to nin pro vi ded pro tec tion in X-ray-in du ced skin da ma ge in rats.…”

mentioning

confidence: 99%

The Protective Effect of Melatonin on the Retinas of Rats with Streptozotocin-Induced Diabetes Mellitus

Ataş¹,

Çıtırık²,

Sönmez³

et al. 2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : To in ves ti ga te the pro tec ti ve ef fect of me la to nin on the re ti nas of rats with strep to zo to cin (STZ)-in du ced di a be tes mel li tus (DM). M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : Thre e gro ups of seven ma le Wis tar rats we re en rol led in this study: (1) a di a be tic gro up, (2) a di a be tic gro up tre a ted with me la to nin, and (3) con trol gro up. Di a be tes was in du ced with a sing le do se of 60 mg/kg in tra pe ri to ne al (i.p). STZ. In addition me la to nin (10 mg/kg/day) was in jec ted i.p. to rats in the tre at ment gro up. All ani mals we re eut ha ni zed 30 days la ter. Oxi da ti ve da ma ge was exami ned by me a su ring re ti nal ma lon di al dehy de (MDA) le vels. R Re e s su ul lt ts s: : The me an MDA le vels in tissu e we ight of re ti nas we re 55.68 ± 6.04 per 100 mg in di a be tic rats in du ced with STZ, 36.13 ± 7.48 per 100 mg in di a be tic rats tre a ted with me la to nin, and 23.04 ± 4.03 per 100 mg tis su e in con trol gro up. Re ti nal MDA le vels we re fo und dif fe rent sig ni fi cantly in both di a be tic gro up and me lato nin-tre a ted di a be tic gro up compared to the con trol gro up (p< 0.001). The re was al so a dif feren ce bet we en the di a be tic and me la to nin-tre a ted di a be tic gro ups for re ti nal MDA le vels (p< 0.01). MDA le vels of di a be tic ani mals tre a ted with me la to nin we re not dif fe rent from con trol gro up (p> 0.05). C Co on nc c l lu u s si i o on n: : Our study re ve a led that the me la to nin im pro ved the re ti nal da mage in di a be tic ma le rats in du ced with STZ and me la to nin had a pro tec ti ve ef fect aga inst the oxida ti ve da ma ge of DM.K Ke ey y W Wo or rd ds s: : Di a be tes mel li tus, ex pe ri men tal; me la to nin; mi toc hon dri al oxi da ti ve da ma ge en do nuc le a se; re ti na Ö ÖZ ZE ET T A Am ma aç ç: : Me la to ni nin strep to zo to sin (STZ) ile uya rıl mış Di a be tes Mel li tus' lu (DM) fa re le rin re ti na la rı üze rin de ki ko ru yu cu et ki si ni in ce le mek tir. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Bu ça lış ma ya di ya betik grup, me la to nin ve ri len di ya be tik grup ve kon trol gru bu ol mak üze re üç gru ba ayır mak su retiy le 21 Wis tar cin si fa re alın dı. Di ya be ti uyar mak için 60 mg/kg STZ tek doz pe ri ton içi ne uy gu lan dı. Ay rı ca te da vi gru bu na me la to nin 10 mg/kg/gün ola rak pe ri ton içi ne uy gu lan dı. Tüm fa re le re 30. gün öte na zi uy gu lan dı. Ok si da tif ha sar, re ti na da öl çü len ma lon di al de hid (MDA) sevi ye si ile be lir len di. B Bu ul l g gu u l la ar r: : Re ti na la rın her 100 mg ıslak ağır lık la rın da ki or ta la ma MDA se viye le ri sı ra sıy la, STZ ile uya rıl mış di ya bet li fa re ler de 55.68 ± 6.04 100 mg, me la to nin ve ri len di ya bet li fa re ler de 36.13 ± 7.48 ve kon trol gru bun da 23.04 ± 4.03 bu lun muş tur. Re ti na MDA sevi ye le ri di ya be tik fa re ler de ve me la to nin ve ri len di ya be tik fa re...

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“…Melatonin binding to calmodulin (Benitez-King et al, 1993;Romero et al, 1998) has been proposed to be responsible for the reduction in rat cerebellum NOS activity induced by this indoleamine, in a nonsaturable manner (Pozo et al, 1997). However, this was not confirmed in cultured endothelial cells, as melatonin did not mimic the effect of calmidazolium (Tamura et al, 2006).…”

mentioning

confidence: 99%

Melatonin inhibits nitric oxide production by microvascular endothelial cells in vivo and in vitro

Silva

Tamura

Macedo

et al. 2007

British J Pharmacology

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Background and purpose: We have previously shown that melatonin inhibits bradykinin-induced NO production by endothelial cells in vitro. The purpose of this investigation was to extend this observation to an in vivo condition and to explore the mechanism of action of melatonin. Experimental approach: RT-PCR assays were performed with rat cultured endothelial cells. The putative effect of melatonin upon arteriolar tone was investigated by intravital microscopy while NO production by endothelial cells in vitro was assayed by fluorimetry, and intracellular Ca 2 þ measurements were assayed by confocal microscopy. Key results: No expression of the mRNA for the melatonin synthesizing enzymes, arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase, or for the melatonin MT 2 receptor was detected in microvascular endothelial cells. Melatonin fully inhibited L-NAME-sensitive bradykinin-induced vasodilation and also inhibited NO production induced by histamine, carbachol and 2-methylthio ATP, but did not inhibit NO production induced by ATP or a, b-methylene ATP. None of its inhibitory effects was prevented by the melatonin receptor antagonist, luzindole. In nominally Ca 2 þ -free solution, melatonin reduced intracellular Ca 2 þ mobilization induced by bradykinin (40%) and 2-methylthio ATP (62%) but not Ca 2 þ mobilization induced by ATP. Conclusions and implications:We have confirmed that melatonin inhibited NO production both in vivo and in vitro. In addition, the melatonin effect was selective for some G protein-coupled receptors and most probably reflects an inhibition of Ca 2 þ mobilization from intracellular stores.

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Inhibition of cerebellar nitric oxide synthase and cyclic GMP production by melatonin via complex formation with calmodulin

Cited by 271 publications

References 39 publications

Melatonin: A pleiotropic molecule regulating inflammation

Melatonin: A pleiotropic molecule regulating inflammation

The Protective Effect of Melatonin on the Retinas of Rats with Streptozotocin-Induced Diabetes Mellitus

Melatonin inhibits nitric oxide production by microvascular endothelial cells in vivo and in vitro

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