Membrane-association and the sensitivity of guanylyl cyclase-coupled receptors to nitric oxide

Nitric oxide (NO) signal transduction occurs through guanylyl cyclase-coupled receptors, which exist in both cytosolic and membranous locations. It has recently been reported from experiments using heart tissue that the membrane-associated receptor has enhanced sensitivity to NO. Owing to its potential importance, we tested this finding using a method of applying NO in known, constant concentrations. The results showed that the concentration-response curves for receptor activation in cytosolic and membrane preparations of two different tissues (cerebellum and platelets) were indistinguishable. In all cases, half-maximal activation required about 1 nM NO and the curves had Hill coefficients of close to 1. The differential sensitivity reported for the heart is attributed to NO being scavenged by myoglobin in the cytosol, but not in the membrane fraction.