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.
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