Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-gamma expression and decrease of PKA activity. Academic Article uri icon

abstract

  • To determine the role and mechanisms of action by which dopaminergic innervation modulates ductal secretion in bile duct-ligated rats, we determined the expression of D1, D2, and D3 dopaminergic receptors in cholangiocytes. We evaluated whether D1, D2 (quinelorane), or D3 dopaminergic receptor agonists influence basal and secretin-stimulated choleresis and lumen expansion in intrahepatic bile duct units (IBDU) and cAMP levels in cholangiocytes in the absence or presence of BAPTA-AM, chelerythrine, 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine (H7), or rottlerin. We evaluated whether 1) quinelorane effects on ductal secretion were associated with increased expression of Ca(2+)-dependent PKC isoforms and 2) increased expression of PKC causes inhibition of PKA activity. Quinelorane inhibited secretin-stimulated choleresis in vivo and IBDU lumen space, cAMP levels, and PKA activity in cholangiocytes. The inhibitory effects of quinelorane on secretin-stimulated ductal secretion and PKA activity were blocked by BAPTA-AM, chelerythrine, and H7. Quinelorane effects on ductal secretion were associated with activation of the Ca(2+)-dependent PKC-gamma but not other PKC isoforms. The dopaminergic nervous system counterregulates secretin-stimulated ductal secretion in experimental cholestasis.

published proceedings

  • Am J Physiol Gastrointest Liver Physiol

author list (cited authors)

  • Glaser, S., Alvaro, D., Roskams, T., Phinizy, J. L., Stoica, G., Francis, H., ... Alpini, G

citation count

  • 66

complete list of authors

  • Glaser, Shannon||Alvaro, Domenico||Roskams, Tania||Phinizy, Jo Lynne||Stoica, George||Francis, Heather||Ueno, Yoshiyuki||Barbaro, Barbara||Marzioni, Marco||Mauldin, Jeremy||Rashid, Sobia||Mancino, Maria Grazia||LeSage, Gene||Alpini, Gianfranco

publication date

  • December 2002