Role of cAMP-PKA-PLC signaling cascade on dopamine-induced PKC-mediated inhibition of renal Na+-K+-ATPase activity

• Tipo: Artigo em Revista Científica Internacional
• Data: 2002

Autores

Pedro Gomes (Autor) Outra; soares-da-silva, p (Autor) FMUP

Revista

Título: American Journal of Physiology - Renal Physiology

Vol. 282

ISSN: 1931-857X

Editora: American Physiological Society

Indexação

ISI Web of Knowledge - 44 Citações

Scopus - 50 Citações

Outras Informações

ID Authenticus: P-000-P2Q

DOI: 10.1152/ajprenal.00318.2001

Abstract (EN): We studied the molecular events set into motion by stimulation of D-1-like receptors downstream of Na+-K+-ATPase, while measuring apical-to-basal ouabain-sensitive, amphotericin B-induced increases in short-circuit current in opossum kidney (OK) cells. The D-1-like receptor agonist SKF-38393 decreased Na+-K+-ATPase activity (IC50, 130 nM). This effect was prevented by the D-1-like receptor antagonist SKF-83566, overnight cholera toxin treatment, the protein kinase A (PKA) antagonist H-89, or the PKC antagonist chelerythrine, but not the mitogen-activated PK inhibitor PD-098059 or phosphatidylinositol 3-kinase inhibitors wortmannin and LY-294002. Dibutyryl cAMP (DBcAMP) and phorbol 12,13-dibutyrate (PDBu) both effectively reduced Na+-K+-ATPase activity. PKA downregulation abolished the inhibitory effects of SKF-38393 and DBcAMP but not those of PDBu. PKC downregulation abolished inhibition by PDBu, SKF-38393, and DBcAMP. The phospholipase C (PLC) inhibitor U-73122 prevented inhibition by SKF-38393 and DBcAMP. However, DBcAMP increased PLC activity. Although OK cells express both G(s)alpha and G(q/11)alpha proteins, D-1-like receptors are coupled to G(s)alpha proteins only, as evidenced by studies in cells treated overnight with specific antibodies raised against G(s)alpha and G(q/11)alpha proteins. We conclude that PLC and Na+-K+-ATPase are effector proteins for PKA and PKC, respectively, after stimulation of D-1-like receptors coupled to G(s)alpha proteins, in a sequence of events that begins with adenylyl cyclase-PKA system activation followed by PLC-PKC system activation.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13