Secretion of gastric mucus phospholipids in response to beta-adrenergic G protein-coupled receptor activation is mediated by SRC kinase-dependent epidermal growth factor receptor transactivation

• Autorzy: Slomiany B.L. , Slomiany A.
• Języki publikacji: EN

Abstrakty

EN

Recent advances in understanding the nature of cellular responses mediated by G protein-coupled receptor (GPCR) activation indicate that integration of the converging regulatory signals into functional cellular pathways requires epidermal growth factor receptor (EGFR) transactivation. In this study, we report that G protein-coupled ß-adrenergic receptor activation leading to stimulation in gastric mucus phospholipid secretion occurs with the involvement of EGFR. Using [14C]choline-labeled gastric mucosal cells in culture, we show that stimulatory effect of ß-adrenergic agonist, isoproterenol, on phospholipid release was subject to a dose-dependent suppression by EGFR kinase inhibitor, PD153035, as well as wortmannin, a specific inhibitor of PI3K. Both inhibitors, moreover, caused the reduction in the gastric mucosal cell phospholipid secretory responses to ß-adrenergic agonist-generated second messenger, cAMP as well as adenyl cyclase activator, forskolin. The gastric mucosal phospholipid secretory responses to isoproterenol, furthermore, were inhibited by PP2, a selective inhibitor of tyrosine kinase Src responsible for ligand-independent EGFR phosphorylation, but not by ERK inhibitor, PD98059. The inhibition of ERK, moreover, did not cause attenuation in phospholipid secretory responses to cAMP and forskolin. The findings underline the central role of EGFR in mediation of gastric mucosal secretory processes, and demonstrate the requirement for Src kinase-dependent EGFR transactivation in regulation of gastric mucosal phospholipid secretion in response to ß-adrenergic GPCR activation.

Słowa kluczowe

EN

receptor transactivation; epidermal growth factor receptor transactivation; coupled receptor; phospholipid secretion; gastric mucus; beta-adrenergic G protein; secretion; phospholipid

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2004
• Tom: 55
• Numer: 3
• Opis fizyczny: p.627-638,fig.,ref.

Twórcy

autor

Slomiany B.L.

• University of Medicine and Dentistry of New Jersey, 110 Bergen Street, P.O.Box 1709, Newark, NJ 07103-2400, USA

autor

Slomiany A.