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Titolo:
D-1-like dopamine receptor activation and natriuresis by nitrocatechol COMT inhibitors
Autore:
Vieira-Coelho, MA; Gomes, P; Serrao, MP; Soares-Da-Silva, P;
Indirizzi:
Fac Med, Inst Pharmacol & Therapeut, Porto, Portugal Fac Med Porto Portugal Med, Inst Pharmacol & Therapeut, Porto, Portugal BIAL, Dept Res & Dev, S Mamede Do Cornoado, Portugal BIAL S Mamede Do Cornoado Portugal Dev, S Mamede Do Cornoado, Portugal
Titolo Testata:
KIDNEY INTERNATIONAL
fascicolo: 5, volume: 59, anno: 2001,
pagine: 1683 - 1694
SICI:
0085-2538(200105)59:5<1683:DDRAAN>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
CATECHOL-O-METHYLTRANSFERASE; NA+-K+-ATPASE; RAT-KIDNEY; ENTACAPONE; TOLCAPONE; PH; STIMULATION; ENTEROCYTES; RO-41-1049; RO-19-6327;
Keywords:
diuretics; sodium transport; renal dopamine; signal transduction; receptor-mediated natriuresis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Soares-Da-Silva, P Fac Med, Inst Pharmacol & Therapeut, Porto, Portugal Fac Med Porto Portugal & Therapeut, Porto, Portugal
Citazione:
M.A. Vieira-Coelho et al., "D-1-like dopamine receptor activation and natriuresis by nitrocatechol COMT inhibitors", KIDNEY INT, 59(5), 2001, pp. 1683-1694

Abstract

Background. In recent years, several nitmcatechol derivatives (tolcapone, entacapone, and nitecapone) have been developed and found to be highly selective and potent inhibitors of catechol-O-methyltransferase (COMT). More recently, natriuretic properties were described for two of these compounds (entacapone and nitecapone), although this was not accompanied by enhanced urinary excretion of dopamine. We hypothesized that nitrocatechol derivativesstimulate D-1-like dopamine receptors. Methods. Adult male Wistar rats were treated with a nitrocatechol COMT inhibitor (entacapone, tolcapone, or nitecapone, 39 mg/kg, orally), and the urinary excretion of dopamine and sodium was quantitated. The interaction of nitrocatechol derivatives with D-1-like receptors was evaluated by their ability to displace [H-3]-Sch23390 binding from membranes of rat renal cortexand cAMP production in opossum kidney (OK) cells. Results. Urinary excretion of sodium (mu mol/h) was markedly increased by all three nitrocatechol derivatives: vehicle, 55.0 +/- 5.6; entacapone, 98.4 +/- 9.3; tolcapone, 97.5 +/- 9.3; and nitecapone, 120.5 +/- 12.6. Pretreatment with the selective, antagonist Sch 23390 (60 mug/kg) tsmpletely prevented their natriuretic effects. Nitecapcane and tolcapone were equipotent (IC50, of 48 and 42 mu mol/L) and more potent than entacapone and dopamine (IC(50)s, of 107 and 279 mu mol/L) in displacing [H-3]-Sch23390 binding. In OK cells, all three nitrocatechol derivatives significantly increased cAMP accumulation and reduced Na+/H+ exchange and Na+,K+-ATPase activities, thisbeing prevented by a blockade of D-1-like receptors. Conclusion. Stimulation of D-1-like dopamine receptors and inhibition of Na+/H+ exchange and Na+,K+-ATPase activities by nitrocatechol COMT inhibitors may contribute to natriuresis produced by these compountls.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 22:05:45