DHA-rich phospholipids optimize G-Protein-coupled signaling.

Objective: To assess the effects of n-3 polyunsaturated phospholipid acyl chains on the initial steps in G-protein-coupled signaling.

Study Design: Isolated components of the visual signal transduction system, rhodopsin, G protein (G(t)), and phosphodiesterase (PDE), were reconstituted in membranes containing various levels of n-3 polyunsaturated phospholipid acyl chains. In addition, rod outer segment disk membranes containing these components were purified from rats raised on n-3-deficient and n-3-adequate diets. The conformation change of rhodopsin, coupling of rhodopsin to G(t), and PDE activity were each measured separately.

Results: The ability of rhodopsin to form the active metarhodopsin II conformation and bind G(t) were both compromised in membranes with reduced levels of n-3 polyunsaturated acyl chains. The activity of PDE, directly related to the integrated cellular response, was reduced in all membranes lacking or deficient in n-3 polyunsaturated acyl chains. PDE activity in membranes containing 22:5n-6 PC was 50% lower than in membranes containing either 22:6n-3 PC or 22:5n-3 PC.

Conclusions: The earliest events in G-protein-coupled signaling; receptor conformation change, receptor-G-protein binding, and PDE activity are reduced in membranes lacking n-3 polyunsaturated acyl chains. Efficient and rapid propagation of G-protein-coupled signaling requires polyunsaturated n-3 phospholipid acyl chains.