D-1-like dopamine receptor activation and natriuresis by nitrocatechol COMT inhibitors

• Tipo: Artigo em Revista Científica Internacional
• Data: 2001

Autores

vieira-coelho, ma (Autor) FMUP; gomes, p (Autor) Outra; serrao, mp (Autor) Outra; soares-da-silva, p (Autor) FMUP

Revista

Título: Kidney International

Vol. 59

Páginas: 1683-1694

ISSN: 0085-2538

Editora: Elsevier

Indexação

ISI Web of Knowledge - 27 Citações

Scopus - 25 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: P-000-VQ8

DOI: 10.1046/j.1523-1755.2001.0590051683.x

Abstract (EN): 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 derivatives stimulate 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 cortex and 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, this being 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12