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 specifically stimulated by alpha(2D/A)-adrenergic receptor (alpha(2D/A)-AR) agonists. The agonists, however, did not stimulate the cyclase activity in the cell-free membranes. It was possible to stimulate the cyclase in cell-free membranes by the addition of the pineal soluble fraction, but this stimulation was Ca2+-dependent and alpha(2D/A)-agonist-independent. It was also possible to achieve Ca2+-dependent stimulation of 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 activator of one of the two members of the ROS-GC subfamily of membrane guanylate cyclases, ROS-GC1. The soluble fraction of the pineal gland stimulated recombinant ROS-GC1 in a Ca2+-dependent fashion. The direct presence of both ROS-GC1 and CD-GCAP in the pineal was established by molecular 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 through intracellular Ca2+ via CD-GCAP.
Venkataraman
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Department of Cell Biology, NJMS, University of Medicine and Dentistry of New Jersey, Stratford 08084, USA.
Duda
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T
Sharma
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RK
D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000502:physiology*; D010870:Pineal Gland / Q000201:enzymology / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015398:Signal Transduction
D018341:Receptors, Adrenergic, alpha-2; D006162:Guanylate Cyclase; D002118:Calcium