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) i n ANF receptor-effector coupling was investigated using cultured bovin e pulmonary artery endothelial cells as a model system. The ligand was equipotent with rANF(99-126) in displacement of [125I]des[Cys105,Cys1 21]rANF(104-126) binding to whole cells and labelled only one populati on 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 o f cGMP was observed under basal conditions, or in the presence of a lo w concentration (0.1 nM) of rANF(99-126). These results provide a mech anistic basis for the observed enhancement of ANF-dependent vasodilata tion by ANF-C receptor selective ligands.