Pedro Gomes

Universidade do Porto

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Patrício Soares‐da‐Silva

Universidade do Porto

Paula Serrão

Universidade do Porto

Sónia Simão

University of Algarve

Elisabete Silva

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto

Maria João Pinho

Norwegian University of Science and Technology

ÂC

Ângela Castela

Université Libre de Bruxelles

Vanda Pinto

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto

Pedro Vendeira

Sociedade Portuguesa de Cardiologia

Flávio Reis

Hospital Pulido Valente

Sara Nunes

University of Lisbon

Cooperative Institutions

Universidade do Porto

University of Coimbra

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto

Instituto de Salud Carlos III

Universidade de Santiago de Compostela

Centro de Investigación Biomédica en Red

Rede de Química e Tecnologia

Instituto de Investigación Sanitaria de Santiago

University of Lisbon

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

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Dopamine D₂‐like receptor‐mediated opening of K⁺ channels in opossum kidney cells

British Journal of Pharmacology (2003)

Pedro Gomes Patrı́cio Soares-da-Silva

This study examined the effects of dopamine D 1 ‐ and D 2 ‐like receptor activation upon basolateral K + ( I K ) currents and changes in membrane potential in opossum kidney (OK) cells. The addition of amphotericin B (3 μg ml −1 ) to the apical side resulted in a rapid increase in I K , this effect being markedly inhibited by the addition of the K + channel blockers barium chloride (1 m M ) or glibenclamide (10 μ M ), but not apamin (1 μ M ). The K + channel opener pinacidil increased the amphotericin B‐induced I K . The selective D 2 ‐like receptor agonist quinerolane increased, in a concentration dependent manner (EC 50 =136 n M ), I K across the basolateral membrane, this effect being abolished by pre‐treatment with pertussis toxin (PTX), S‐sulpiride (selective D 2 ‐like receptor antagonist) and glibenclamide. The selective D 1 ‐like receptor agonist SKF 38393 did not change I K . Both H‐89 (PKA inhibitor) and chelerythrine (PKC inhibitor) failed to prevent the stimulatory effect of quinerolane upon I K . Quinerolane did not change basal levels of cyclic AMP and also failed to affect the forskolin‐induced increase in cyclic AMP levels. The stimulation of D 2 ‐like receptor was associated with a rapid hyperpolarizing effect, whereas D 1 ‐like receptor activation was accompanied by increases in cell membrane potential. The hyperpolarizing effect of quinerolane (EC 50 =129 n M ) was prevented by pre‐treatment with PTX, S‐sulpiride and glibenclamide. It is concluded that stimulation of dopamine D 2 ‐like, but not D 1 ‐like, receptors coupled to PTX‐sensitive G proteins of the G i/o class produce membrane hyperpolarization through opening of K ATP channels. British Journal of Pharmacology (2003) 138 , 968–976. doi: 10.1038/sj.bjp.0705125

Apamin

Sulpiride

10.1038/sj.bjp.0705125

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Citations (7)

Increased responsiveness to JNK1/2 mediates the enhanced H2O2-induced stimulation of Cl−/HCO3− exchanger activity in immortalized renal proximal tubular epithelial cells from the SHR

Biochemical Pharmacology (2010)

Sónia Simão Pedro Gomes Pedro A. José Patrı́cio Soares-da-Silva

Apocynin

Sodium–hydrogen antiporter

10.1016/j.bcp.2010.05.013

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Citations (7)

Experimental Gerontology (2011)

Sónia Simão Pedro Gomes Vanda Pinto Elisabete Silva João S. Amaral

NOX4

SOD2

P22phox

TBARS

10.1016/j.exger.2011.02.003

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Citations (37)

Na+-Independent Transporters, LAT-2 and b0,+, Exchange L-DOPA with Neutral and Basic Amino Acids in Two Clonal Renal Cell Lines

The Journal of Membrane Biology (2002)

Pedro Gomes Patrı́cio Soares-da-Silva

Efflux

10.1007/s00232-001-0136-8

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Citations (36)

D₂-like receptor-mediated inhibition of Na⁺-K⁺-ATPase activity is dependent on the opening of K⁺channels

AJP Renal Physiology (2002)

Pedro Gomes Patrı́cio Soares-da-Silva

This study examined the effects of D 2 -like dopamine receptor activation on Na + -K + -ATPase activity while apical-to-basal, ouabain-sensitive, amphotericin B-induced increases in short-circuit current and basolateral K + ( I K ) currents in opossum kidney cells were measured. The inhibitory effect of dopamine on Na + -K + -ATPase activity was completely abolished by either D 1 - or D 2 -like receptor antagonists and mimicked by D 1 - and D 2 -like receptor agonists SKF-38393 and quinerolane, respectively. Blockade of basolateral K + channels with BaCl 2 (1 mM) or glibenclamide (10 μM), but not apamin (1 μM), totally prevented the inhibitory effects of quinerolane. The K + channel opener pinacidil decreased Na + -K + -ATPase activity. The inhibitory effect of quinerolane on Na + -K + - ATPase activity was abolished by pretreatment of opossum kidney cells with pertussis toxin (PTX). Quinerolane increased I K across the basolateral membrane in a concentration-dependent manner; this effect was abolished by pretreatment with PTX, S-sulpiride, and glibenclamide. SKF-38393 did not change I K . Both H-89 (protein kinase A inhibitor) and chelerythrine (protein kinase C inhibitor) failed to prevent the stimulatory effect of quinerolane on I K . The stimulation of the D 2 -like receptor was associated with a rapid hyperpolarizing effect, whereas D 1 -like receptor activation was accompanied by increases in cell membrane potential. It is concluded that stimulation of D 2 -like receptors leads to inhibition of Na + -K + -ATPase activity and hyperpolarization; both effects are associated with the opening of K + channels.

Hyperpolarization

Apamin

10.1152/ajprenal.00244.2001

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Citations (25)

Ingestion of a natural mineral-rich water in an animal model of metabolic syndrome: effects in insulin signalling and endoplasmic reticulum stress

Hormone Molecular Biology and Clinical Investigation (2016)

Cidália Pereira Emanuel Passos Mílton Severo Isabel Vitó Xiaogang Wen

High-fructose and/or low-mineral diets are relevant in metabolic syndrome (MS) development. Insulin resistance (IR) represents a central mechanism in MS development. Glucocorticoid signalling dysfunction and endoplasmic reticulum (ER) and oxidative stresses strongly contribute to IR and associate with MS. We have described that natural mineral-rich water ingestion delays fructose-induced MS development, modulates fructose effects on the redox state and glucocorticoid signalling and increases sirtuin 1 expression. Here, we investigated mineral-rich water ingestion effects on insulin signalling and ER homeostasis of fructose-fed rats.Adult male Sprague-Dawley rats had free access to standard-chow diet and different drinking solutions (8 weeks): tap water (CONT), 10%-fructose/tap water (FRUCT) or 10%-fructose/mineral-rich water (FRUCTMIN). Hepatic and adipose (visceral, VAT) insulin signalling and hepatic ER homeostasis (Western blot or PCR) as well as hepatic lipid accumulation were evaluated.Hepatic p-IRS1Ser307/IRS1 (tendency), p-IRS1Ser307, total JNK and (activated IRE1α)/(activated JNK) decreased with fructose ingestion, while p-JNK tended to increase; mineral-rich water ingestion, totally or partially, reverted all these effects. Total PERK, p-eIF2α (tendency) and total IRS1 (tendency) decreased in both fructose-fed groups. p-ERK/ERK and total IRE1α increasing tendencies in FRUCT became significant in FRUCTMIN (similar pattern for lipid area). Additionally, unspliced-XBP1 increased with mineral-rich water. In VAT, total ERK fructose-induced increase was partially prevented in FRUCTMIN.Mineral-rich water modulation of fructose-induced effects on insulin signalling and ER homeostasis matches the better metabolic profile previously reported. Increased p-ERK/ERK, adding to decreased IRE1α activation, and increased unspliced-XBP1 and lipid area may protect against oxidative stress and IR development in FRUCTMIN.

IRS1

10.1515/hmbci-2015-0033

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Citations (11)

Long-term food restriction attenuates age-related changes in the expression of renal aldosterone-sensitive sodium transporters in Wistar-Kyoto rats: A comparison with SHR

Experimental Gerontology (2012)

Vanda Pinto Maria João Pinho Elisabete Silva Sónia Simão Bruno Igreja

Mineralocorticoid

Renal cortex

10.1016/j.exger.2012.05.022

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Citations (3)

SIRT2

Springer eBooks (2016)

Pedro Gomes

10.1007/978-1-4614-6438-9_101725-1

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Citations (0)

Disfunção erétil na diabetes – avaliação de alterações moleculares induzidas pelo stresse oxidativo

Acta Urológica Portuguesa (2015)

Ângela Castela Pedro Gomes Valentina F. Domingues Paula Paíga Raquel Costa

A disfunção erétil (DE) apresenta‐se como uma das complicações mais comuns da diabetes, sendo o stresse oxidativo uma característica relevante da DE diabética. Eventos deletérios induzidos pelo stresse oxidativo levam a relevantes alterações celulares e tecidulares alvos do dano oxidativo. No entanto, permanecem por clarificar os efeitos nocivos de mecanismos oxidativos no tecido peniano com a progressão da diabetes. Desta forma, pretendeu‐se avaliar a condição do stresse oxidativo a nível sistémico e peniano numa fase precoce e estabelecida da diabetes. Ratos machos Wistar foram divididos em grupos de: 2 e 8 semanas de diabetes tipo 1 induzida por streptozotocina e os respetivos controlos emparelhados pela idade. O stresse oxidativo sistémico foi avaliado pela quantificação de peróxido de hidrogénio (H2O2) na urina e pelo rácio glutationa reduzida/oxidada (GSH/GSSG) no plasma. Localmente, em tecido peniano, a condição de stresse oxidativo foi analisada através da produção de H2O2 e avaliação da nitração proteica pela deteção de 3‐nitrotirosina (3‐NT). 3‐NT foi quantificado por western blotting e por imunohistoquímica identificouse a sua localização celular no tecido cavernoso dos animais em estudo. A avaliação sistémica do stresse oxidativo revelou um aumento significativo dos níveis de H2O2 urinário e uma diminuição significativa do rácio GSH/GSSG circulante nos animais com uma diabetes avançada. No tecido cavernoso, o incremento significativo da produção de H2O2 verificou‐se também nos animais com 8 semanas de diabetes. Relativamente à formação de 3‐NT, os dados obtidos revelaram um aumento significativo no tecido cavernoso em animais com uma diabetes tardia e uma localização predominante deste marcador oxidativo na musculatura lisa cavernosa. Os resultados indicam um efeito nocivo sistémico e cavernoso induzido pelo stresse oxidativo, proeminente num estadio avançado da diabetes. Sugere‐se que o aumento das modificações oxidativas nas proteínas do pénis poderá ser responsável por promover desregulações estruturais/funcionais nos mecanismos celulares/moleculares, contribuindo para o desenvolvimento e progressão da DE associada à diabetes. Erectile dysfunction (ED) is one of the most common complications of diabetes, being oxidative stress an important feature of diabetic ED. Deleterious events induced by oxidative stress lead to crucial cellular and tissue alterations targeted by oxidative lesions. However, the noxious effects of oxidative stress mechanisms in penile tissue with the progression of diabetes, remains unclear. We intended to evaluate systemic and penile oxidative stress in an early and late stage of diabetes. Male Wistar rats were divided in groups: 2 and 8‐weeks of streptozotocin‐induced type 1 diabetes, and age‐matched controls. Systemic oxidative stress was evaluated in urine by hydrogen peroxide (H2O2) quantification and in plasma by reduced/oxidized glutathione (GSH/GSSG) ratio. Penile oxidative status was assessed by H2O2 production and by the evaluation of protein nitration through the detection of 3‐nitrotyrosine (3‐NT). 3‐NT was quantified by Western blotting analysis and immunohistochemistry allowed to identify its cavernosal cellular location. Systemic evaluation revealed a significant increase in urinary H2O2 levels in both diabetic groups. A significant decrease of circulating GSH/GSSG ratio was observed in animals with late stage diabetes. In cavernosal tissue, H2O2 production was significantly increased at 8‐weeks diabetes. Regarding 3‐NT cavernosal formation, data revealed a significant increment in advanced diabetes and a predominant location in cavernosal smooth muscle cells. We observed that systemic and cavernosal noxious effects induced by oxidative stress are predominant in advanced diabetes. Increased penile protein oxidative modifications in late‐staged diabetes may be responsible for structural/functional deregulations in cellular/molecular systems, contributing to the development of diabeticassociated ED.

10.1016/j.acup.2015.01.002

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D1-like dopamine receptor activation and natriuresis by nitrocatechol COMT inhibitors

Kidney International (2001)

Maria Augusta Vieira‐Coelho Pedro Gomes Paula Serrão Patrı́cio Soares-da-Silva

10.1046/j.1523-1755.2001.0590051683.x

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Citations (26)