cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis

MANY hormones or neurotransmitters act at cell surface receptors to increase the intracellular free calcium concentration, triggering a wide range of cellular responses1. As the source of this Ca2+ is often internal stores, additional messengers are required to convey the hormonal message from the plasma membrane. Cyclic ADP-ribose (cADPR) has been proposed as the endogenous activator of Ca2+-induced Ca2+ release by the ryanodine receptor in sea urchin eggs and in several mammalian cell types2–8,22. A second messenger role for cADPR requires that its intracellular levels be under the control of extracellular stimuli. Here we demonstrate a novel action of 3',5'-cyclic guanosine monophosphate (cGMP) in stimulating the synthesis of cADPR from β-NAD+ by activating its synthetic enzyme ADP-ribosyl cyclase9–11 in sea urchin eggs and egg homogenates. We suggest that cADPR may transduce signals generated by cell surface receptors or gaseous transmitters linked to cGMP production.

[1]  F. Hofmann,et al.  Diastereomers of adenosine 3',5'-monothionophosphate (cAMP[S]) antagonize the activation of cGMP-dependent protein kinase. , 1985, European journal of biochemistry.

[2]  H. C. Lee,et al.  Widespread occurrence in animal tissues of an enzyme catalyzing the conversion of NAD+ into a cyclic metabolite with intracellular Ca2+-mobilizing activity. , 1989, The Journal of biological chemistry.

[3]  R. Nuccitelli,et al.  Mechanisms of Egg Activation , 2013, Springer US.

[4]  H. C. Lee,et al.  Comparison of Ca2+ mobilizing activities of cyclic ADP-ribose and inositol trisphosphate. , 1990, Cell regulation.

[5]  M. Poenie.  Alteration of intracellular Fura-2 fluorescence by viscosity: a simple correction. , 1990, Cell calcium.

[6]  B. Jastorff,et al.  Inhibition of cGMP‐dependent protein kinase by (Rp)‐guanosine 3',5'‐monophosphorothioates , 1990, FEBS letters.

[7]  L. Jaffe.  The path of calcium in cytosolic calcium oscillations: a unifying hypothesis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[8]  F. Strumwasser,et al.  Purification and characterization of a molluscan egg-specific NADase, a second-messenger enzyme. , 1991, Cell regulation.

[9]  A. Galione,et al.  Ca(2+)-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose , 1991, Science.

[10]  Hon Cheung Lee,et al.  ADP-ribosyl cyclase: an enzyme that cyclizes NAD+ into a calcium-mobilizing metabolite. , 1991, Cell regulation.

[11]  T. Whalley,et al.  Internal calcium release and activation of sea urchin eggs by cGMP are independent of the phosphoinositide signaling pathway. , 1992, Molecular biology of the cell.

[12]  A. Galione.  Ca(2+)-induced Ca2+ release and its modulation by cyclic ADP-ribose. , 1992, Trends in pharmacological sciences.

[13]  B. Potter.  Synthetic Analogs of Intracellular Messengers , 1992 .

[14]  K. Swann,et al.  Activation of Ca(2+)-dependent currents in cultured rat dorsal root ganglion neurones by a sperm factor and cyclic ADP-ribose. , 1992, Molecular biology of the cell.

[15]  S. Takasawa,et al.  Cyclic ADP-ribose in insulin secretion from pancreatic beta cells. , 1993, Science.

[16]  M. Berridge.  Inositol trisphosphate and calcium signalling , 1993, Nature.

[17]  A. Chu,et al.  Cyclic ADP-ribose as an endogenous regulator of the non-skeletal type ryanodine receptor Ca2+ channel , 1993, Nature.

[18]  Hon Cheung Lee,et al.  Potentiation of calcium- and caffeine-induced calcium release by cyclic ADP-ribose. , 1993, The Journal of biological chemistry.

[19]  A. Galione,et al.  Cyclic ADP‐ribose‐induced Ca2+ release from rat brain microsomes , 1993, FEBS letters.

[20]  A. Galione.  Cyclic ADP-ribose: a new way to control calcium. , 1993, Science.

[21]  K. Swann,et al.  Lighting the fuse at fertilization , 1993 .