Effects of the ANF-C receptor ligand des[Cys105,Cys121]rANF(104-126) on ANF internalization and cGMP production by bovine pulmonary artery endothelial cells.
A role for the ANF-C receptor ligand des[Cys105,Cys121]rANF(104-126) in ANF receptor-effector coupling was investigated using cultured bovine pulmonary artery endothelial cells as a model system. The ligand was equipotent with rANF(99-126) in displacement of [125I]des[Cys105,Cys121]rANF(104-126) binding to whole cells and labelled only one population of ANF receptors as shown by affinity crosslinking experiments. In cells pretreated with des[Cys105, Cys121]rANF(104-126), internalization of [125I]rANF(99-126) binding was reduced and enhanced accumulation of cGMP was observed under basal conditions, or in the presence of a low concentration (0.1 nM) of rANF(99-126). These results provide a mechanistic basis for the observed enhancement of ANF-dependent vasodilation by ANF-C receptor selective ligands.
Smyth
E M
EM
Department of Pharmacology, University College, Belfield, Dublin, Ireland.
Keenan
A K
AK
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology*; D011651:Pulmonary Artery; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D010446:Peptide Fragments; D011994:Recombinant Proteins; C056607:atriopeptin analog I; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP