THE ALPHA(2D A)-ADRENERGIC RECEPTOR-LINKED MEMBRANE GUANYLATE-CYCLASE- A NEW SIGNAL-TRANSDUCTION SYSTEM IN THE PINEAL-GLAND/

In the pineal gland, the membrane guanylate cyclase activity was speci fically stimulated by alpha(2D/A)-adrenergic receptor (alpha(2D/A)-AR) agonists, The agonists, however, did not stimulate the cyclase activi ty in the fell-free membranes. It was possible to stimulate the cyclas e in cell-free membranes by the addition of the pineal soluble fractio n, but this stimulation was Ca2+-dependent and alpha(2D/A)-agonist-ind ependent. It was also possible to achieve Ca2+-dependent stimulation o f the cyclase by the direct addition of CD-GCAP to the isolated pineal membranes. CD-GCAP is a Ca2+-binding protein and is a specific activa tor of one of the two members of the ROS-GC subfamily of membrane guan ylate cyclases, ROS-GC1. The soluble fraction of the pineal gland stim ulated recombinant ROS-GC1 in a Ca2+ dependent fashion. The direct pre sence of both ROS-GC1 and CD-GCAP in the pineal was established by mol ecular cloning/PCR studies, The findings demonstrate the existence of a novel signal transduction mechanism - the linkage of the alpha(2D/A) -AR signaling system with ROS-GC1 transduction system, occurring throu gh intracellular Ca2+ via CD-GCAP, (C) 1998 Federation of European Bio chemical Societies.