The influence of isatin on guanylyl cyclase of rat heart membranes

Медведев, А. Е.; Sandler, M.; Glover, Vivette

doi:10.1016/s0014-2999(99)00688-3

Cited by 15 publications

(6 citation statements)

References 12 publications

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“…Isatin is an endogenously occurring compound that can inhibit natriuretic peptide receptor activation (Glover et al, 1995) possibly by allosteric means (Medvedev et al, 1998(Medvedev et al, , 1999. Although isatin alone exerted no appreciable effect on outflow facility in the rabbit, it antagonized the ability of BRE to increase outflow facility.…”

Section: Discussionmentioning

confidence: 99%

Bremazocine Increases C-Type Natriuretic Peptide Levels in Aqueous Humor and Enhances Outflow Facility

Potter¹,

Russell²,

Manhiani³

2004

J Pharmacol Exp Ther

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A relatively selective agonist of opioid receptors (KOR), bremazocine (BRE), lowers intraocular pressure in rabbits, in part, by increasing natriuretic peptide levels in aqueous humor and by enhancing total outflow facility (TOF). Natriuretic peptide (NP) levels [atrial NP (ANP), brain NP (BNP), and C-type NP (CNP)] were measured in aqueous humor of rabbits either by radioimmunoassay or enzyme immunoassay. TOF was determined in rabbits by two-level constant pressure perfusion of the anterior chamber. Experimental regimens included topical treatment with BRE in the presence or absence of KOR antagonist (norbinaltorphimine), protein kinase C inhibitor (chelerythrine), and natriuretic peptide receptor antagonist (isatin). The rank order of basal NP levels in aqueous humor of rabbits was BNP & CNP Ͼ ANP. Topical administration of BRE (1-100 g) caused dose-related elevations of CNP levels in aqueous humor that were inhibited by topical pretreatment with either norbinaltorphimine (100 g, bilaterally) or chelerythrine (10 g, bilaterally). Topically administered BRE (100 g) also elevated levels of ANP and BNP in aqueous humor and evoked an 80% increase in TOF. The increase in TOF was antagonized by topical pretreatment with either norbinaltorphimine (100 g, bilaterally) or isatin (100 g, bilaterally). Bremazocine induced an increase in NP (ANP, BNP, and CNP) levels and TOF in rabbits by activating KOR. The increase in CNP levels elicited by BRE was inhibited by norbinaltorphimine and chelerythrine; therefore, this event is most likely mediated by a KOR-linked activation of protein kinase C. These data provide evidence that the increase in TOF elicited by BRE was mediated by a KORactivated paracrine effect of NPs on tissues within ocular outflow tract(s).Neuroendocrine regulation of fluid homeostasis throughout the body depends, in part, on the activity of the natriuretic peptide system. Of the three natriuretic peptides [i.e., atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)], the sequences of ANP and CNP are more highly conserved among the species, whereas the structure of BNP varies greatly. It has been proposed that natriuretic peptides generated within the eye contribute to the regulation of aqueous humor dynamics; however, the understanding of how this ocular neuroendocrine system is modulated is very limited.Recently, molecular evidence has been presented for neuroendocrine functions in the ciliary epithelium Ortego and Coca-Prados, 1999). Moreover, it has been postulated that natriuretic peptides released by drugs from ciliary epithelial cells could then act in an autocrine and/or paracrine manner to change intraocular pressure (IOP). Recent reports have shown that ocular hypotensive drugs such as opioid receptor (KOR) agonists (bremazocine) (Russell et al., 2001;Russell and Potter, 2002) and imidazoline-1/␣2 agonists (Ogidigben et al., 1999(Ogidigben et al., , 2002 elevate ANP levels in aqueous humor of rabbits.The current study was conducted to: 1) ...

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Section: Discussionmentioning

confidence: 99%

Bremazocine Increases C-Type Natriuretic Peptide Levels in Aqueous Humor and Enhances Outflow Facility

Potter¹,

Russell²,

Manhiani³

2004

J Pharmacol Exp Ther

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“…Изатин в физиологических концентрациях (в диапазоне от 1 нМ до 10 мкМ) является ингибитором моноаминоксидазы (МАО) Б [8], эндогенным ингибитором стимулируемой натрийуретическими пептидами мембраносвязанной гуанилатциклазы [9,10]; он также тормозит индуцированную нитропруссидом натрия активацию растворимой гуанилатциклазы [11].…”

Section: * -адресат для перепискиunclassified

Potentiation of NO-dependent activation of soluble guanylyl cyclase by 5-nitroisatin and antiviral preparatation arbidol

Is¹,

AIu²,

Ae³

2013

BIOMED KHIM

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Учреждение Российской академии медицинских наук, Научно-исследовательский институт биомедицинской химии имени В.Н. Ореховича РАМН, Погодинская ул., 10, 119121 Москва; факс: (499)245-0857; эл. почта: professor57@yandex.ru Изатин (индол-дион) -эндогенный индол, обладающий широким спектром биологической и фармакологической активности. Исследовано влияние производных изатина -5-нитроизатина и арбидола (противовирусного препарата) на индуцированную спермин NONO активацию растворимой гуанилатциклазы тромбоцитов человека. 5-нитроизатин и арбидол не влияли на базальную активность, но синергично увеличивали концентрационно-зависимым образом индуцированную спермин NONO активацию этого фермента. 5-нитроизатин и арбидол, аналогично YC-1, повышали чувствительность гуанилатциклазы к оксиду азота (NO) и осуществляли сдвиг влево кривой зависимости активации фермента от концентрации спермин NONO. В то же время, использованные соединения не изменяли синергичного увеличения индуцированной спермин NONO активации растворимой гуанилатциклазы в присутствии YC-1. Это свидетельствует о том, что 5-нитроизатин и арбидол не конкурировали с YC-1. Добавление изатина не изменяло синергичного увеличения индуцированной спермин NONO активации гуанилатциклазы 5-нитроизатином и арбидолом и не влияло на сдвиг влево кривой зависимости активации фермента этими соединениями от концентрации спермин NONO. Эти данные свидетельствуют об отсутствии конкуренции между изатином и двумя использовнными его производными.

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“…1) is an endogenous compound found in the brain, heart, kidney and other tissues at concentrations of 1–10 µg/g tissue 2 . Isatin directly inhibits atrial natriuretic peptide (ANP)‐stimulated guanylyl cyclase (GC) 3–6 . Natriuretic peptides are involved in the regulation of natriuresis and blood pressure 7 and isatin may be a physiological regulator of the natriuretic peptide receptor (NPR) 2,8,9 .…”

Section: Introductionmentioning

confidence: 99%

“…Isatin inhibits GC stimulation by blocking the binding of ANP to the NPR‐A receptor, resulting in reduced levels of cGMP 3–5 . The isatin‐mediated decrease in cGMP levels leads to lower cGMP‐dependent protein kinase activity and an overall decrease in the phosphorylation of intracellular proteins 6 . Therefore, isatin treatment leads to alterations in a diverse set of cellular responses that are regulated via the phosphorylation of enzymes and ion channels induced by cGMP 7,10 .…”

Section: Introductionmentioning

confidence: 99%

Vasodilatory Activity of Novel Carbamate Derivatives of Isatin

Maronas

Sudo

Côrrea

et al. 2008

Clin Exp Pharma Physio

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Isatin (1H-indole-2,3 dione) is an endogenous compound that may act as a physiological regulator of muscle contraction by reducing cGMP production by inhibition of guanylyl cyclase (GC) activity. Intracellular cGMP levels can regulate the contractile response of smooth muscle. Therefore, in the present study we investigated the effects of seven novel carbamate derivatives of isatin, namely C1-C7, on the contractility of aortic rings from Wistar rats. Carbamates C1 and C6 most effectively promoted endothelium-dependent relaxation of aortic rings pretreated with 10 micromol/L phenylephrine (PE) to induce contraction. The concentration of the C1 and C6 carbamates necessary to reduce PE-induced aortic contraction by 50% (IC(50)) was 5.6 +/- 1.0 and 48.4 +/- 3.4 micromol/L, respectively. Carbamate derivative-induced vasodilation required an intact endothelium, which is responsible for nitric oxide (NO) release. Pretreatment of rings with 100 micromol/L naloxone or 10 micromol/L atropine prevented the C1- and C6-mediated vascular relaxation, indicating that the vasodilatory activity was dependent on the activation of opioid or muscarinic receptors, respectively. The results of our studies provide insights into the role of novel carbamates in the regulation of vascular tone. Carbamates could stimulate NO synthesis, which induces vasodilation primarily by stimulation of GC and cGMP production. Taken together, our findings suggest that carbamate derivative-induced vasodilation may be considered an alternative treatment for primary and/or secondary hypertension.

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The influence of isatin on guanylyl cyclase of rat heart membranes

Cited by 15 publications

References 12 publications

Bremazocine Increases C-Type Natriuretic Peptide Levels in Aqueous Humor and Enhances Outflow Facility

Bremazocine Increases C-Type Natriuretic Peptide Levels in Aqueous Humor and Enhances Outflow Facility

Potentiation of NO-dependent activation of soluble guanylyl cyclase by 5-nitroisatin and antiviral preparatation arbidol

Vasodilatory Activity of Novel Carbamate Derivatives of Isatin

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