Tools for investigating functional interactions between lipid-derived autacoids and their receptors

MR Lerner, L Golovyan, GF Graminski… - American Journal of …, 1996 - journals.lww.com
MR Lerner, L Golovyan, GF Graminski, K Harris, L Huang, CK Jayawickreme, S Karne
American Journal of Therapeutics, 1996journals.lww.com
A method for rapidly evaluating functional interactions between ligands and G-protein-
coupled receptors has been developed. The technology is based on the ability of animals to
change color by controlling the position of pigmented organelles within skin cells called
melanophores. cDNA coding for a receptor to be studied is expressed in immortalized frog
melanophores. Stimulation of a receptor that normally functions to activate either adenyl
cyclase or phospholipase C induces centrifugal melanosome translocation and cell …
Abstract
A method for rapidly evaluating functional interactions between ligands and G-protein-coupled receptors has been developed. The technology is based on the ability of animals to change color by controlling the position of pigmented organelles within skin cells called melanophores. cDNA coding for a receptor to be studied is expressed in immortalized frog melanophores. Stimulation of a receptor that normally functions to activate either adenyl cyclase or phospholipase C induces centrifugal melanosome translocation and cell darkening. Conversely, application of an agonist to cells expressing a receptor that operates to inhibit adenyl cyclase induces centripetal pigment movement and cell lightening. The simple optical change can be used to investigate ligand-receptor interactions at several levels, including single-cell analysis and high-throughput chemical screening. Current efforts are focused on (1) identifying small peptides that activate or block thromboxane A 2 and platelet-activating factor (PAF) receptors and (2) cloning eicosanoid receptors.
Lippincott Williams & Wilkins