Iloprost-induced desensitization of the prostacyclin receptor in isolated rabbit lungs.

Background: The rapid desensitization of the human prostacyclin (IP) in response to agonist binding has been shown in cell culture. Phosphorylation of the IP receptor by protein kinase C (PKC) has been suggested to be involved in this process.

Methods And Results: In this study we investigated the vasodilatory effects of iloprost, a stable prostacyclin analogue, in perfused rabbit lungs.

Long-term-desensitization of prostacyclin receptors is independent of the C-terminal tail.

Persistent stimulation of the G(s) protein-coupled prostacyclin receptor (IP-R) causes its slow desensitization in a variety of cell types, a significant desensitization requiring several hours. To evaluate the role of the human IP-R C-terminus in desensitization and agonist-induced internalization, a C-terminally truncated hIP-receptor was generated. The C-terminal 68 amino acid residues were deleted by introduction of a stop codon for exchange of the original S319 codon (termed D318 mutant).