DIFFERENTIAL REGULATION OF NICOTINIC-ACID ADENINE-DINUCLEOTIDE PHOSPHATE AND CADP-RIBOSE PRODUCTION BY CAMP AND CGMP

The sea urchin egg has been used as a system to study calcium-release mechanisms induced by inositol 1,4,5-trisphosphate (IP3), cADP-ribose (cADPR), and more recently, nicotinic acid-adenine dinucleotide phosph ate (NAADP). In order that cADPR and NAADP may be established as endog enous messengers for calcium release, the existence of intracellular e nzymes capable of metabolizing these molecules must be demonstrated. I n addition, intracellular levels of cADPR and NAADP should be under th e control of extracellular stimuli. It has been shown that cGMP stimul ates the synthesis of cADPR in the sea urchin egg. The present study s hows that the sea urchin egg is capable of synthesizing and degrading NAADP. cADPR and NAADP synthetic activities appear to be separate, wit h different cellular localizations, pH and temperature optima. We sugg est that in the sea urchin egg, cADPR and NAADP production may be diff erentially regulated by receptor-coupled second messengers, with cADPR production being regulated by cGMP and NAADP production modulated by cAMP.