Regulation of Cl- secretion by alpha-adrenergic receptors in mouse colonic epithelium

• Tipo: Artigo em Revista Científica Internacional
• Data: 2003

Autores

lam, rs (Autor) Outra; app, em (Autor) Outra; nahirney, d (Autor) Outra; szkotak, aj (Autor) Outra; vieira-coelho, ma (Autor) FMUP; king, m (Autor) Outra; duszyk, m (Autor) Outra

Revista

Título: JOURNAL OF PHYSIOLOGY-LONDON

Vol. 548

Páginas: 475-484

ISSN: 0022-3751

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 28 Citações

Scopus - 27 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-000-H29

DOI: 10.1113/jphysiol.2002.036806

Abstract (EN): Previous studies have shown that a, adrenoceptor (alpha(2)AR) agonists inhibit electrolyte secretion in colonic epithelia, but little is known about the molecular mechanisms involved in this process. In this study we examined the effect Of a2AR activation on transepithelial anion secretion across isolated murine colonic epithelium. We found that alpha(2)AR agonists, UK 14,304, clonidine and medetomidine were potent inhibitors of anion secretion, especially in the proximal colon. Short circuit current measurements (I-sc) in colonic epithelia from normal and cystic fibrosis (CF) mice showed that alpha(2)AR agonists; inhibited basal cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl- secretion but had no effect on CFTR activation by cAMP-dependent phosphorylation. Apical administration of an ionophore, nystatin (90 mug ml(-1)), was used to investigate the effect of UK 14,304 on basolateral K+ transport. The Na+-K+-ATPase current, measured as ouabain-sensitive current in the absence of ion gradients, was unaltered by pretreatment of the tissue with UK 14,304 (1 muM). In the presence of a basolaterally directed K+ gradient, UK 14,304 significantly reduced nystatin-activated I-sc indicating that activation of alpha(2)ARs inhibits basolateral K+ channels. Studies with selective K+ channel inhibitors and openers showed that alpha(2)AR agonists inhibited K-ATP channels that were tonically active in mouse colonic epithelia. RTPCR and pharmacological studies suggested that these channels could be similar to vascular smooth muscle K-ATP channels comprising Kir6.1/SUR2B or Kir6.2/SUR2B subunits. Inhibition of anion secretion by alpha(2)AR agonists required activation of pertussis toxin-sensitive G(i/o). proteins, but did not involve classical second messengers, such as cAMP or Ca2+. In summary, alpha(2)ARs inhibit anion secretion in colonic epithelia by acting on basolateral K-ATP channels, through a process that does not involve classical second messengers.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10