scholarly journals From Eggs to Hearts: What Is the Link between Cyclic ADP-Ribose and Ryanodine Receptors?

2010 ◽  
Vol 30 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Elisa Venturi ◽  
Samantha Pitt ◽  
Elena Galfré ◽  
Rebecca Sitsapesan
Keyword(s):  
Ryanodine Receptors ◽  
Cyclic Adp Ribose

The existence of inositol 1,4,5-trisphosphate and ryanodine receptors in mature bovine oocytes

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2645-2654 ◽  
Author(s):  
C. Yue ◽  
K.L. White ◽  
W.A. Reed ◽  
T.D. Bunch
Keyword(s):  
Ryanodine Receptors ◽  
Inhibitory Effect ◽  
Ruthenium Red ◽  
Calcium Oscillations ◽  
Ip3 Receptor ◽  
Cyclic Adp Ribose ◽  
Inositol 1,4,5 Trisphosphate ◽  
Bovine Oocytes ◽  
Continuous Injection

Intracellular Ca2+ (Ca2+i) transients during fertilization are critical to the activation of eggs in all species studied. Activation of both the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and ryanodine receptor (RYR) are responsible for the calcium oscillations during fertilization in sea urchin eggs. Using in vitro matured bovine oocytes loaded with Fura-2 AM ester as Ca2+i indicator, we addressed whether IP3Rs and RYRs coexist in mammalian eggs. Our results indicate that microinjection of 50–250 nM IP3 or 10–20 mM caffeine, 100–200 microM ryanodine and 4–8 microM cyclic ADP-ribose all induced Ca2+i release. The Ca2+i release induced by 250 nM IP3 could only be inhibited by prior injection of 1 mg/ml heparin which was overcome by continuous injection of IP3 to 1 microM. Prior injection of either 50 microM ruthenium red, 50 microM procaine or 1 % vehicle medium (VM) did not affect the Ca2+i release induced by IP3. Prior injection of heparin or VM did not affect the Ca2+i release induced by 10–20 mM caffeine or 200 microM ryanodine, but prior injection of 50 microM ruthenium red or procaine completely inhibited the effect of 10–20 mM caffeine. In addition, continuous injection of caffeine up to 40 mM overcame the inhibitory effect of ruthenium red or procaine. The same 50 microM concentration of ruthenium red or procaine only partially blocked the effect of 200 microM ryanodine, but 200 microM ruthenium red or procaine completely blocked the effect of 200 microM ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of mouse egg activation: presence of ryanodine receptors and effects of microinjected ryanodine and cyclic ADP ribose on uninseminated and inseminated eggs

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2233-2244 ◽  
Author(s):  
T. Ayabe ◽  
G.S. Kopf ◽  
R.M. Schultz
Keyword(s):  
Ryanodine Receptor ◽  
Ryanodine Receptors ◽  
Meiotic Spindle ◽  
Egg Activation ◽  
Dependent Manner ◽  
Cyclic Adp Ribose ◽  
Inositol 1,4,5 Trisphosphate ◽  
Mouse Egg

Sperm-induced activation of mammalian eggs is associated with a transient increase in Ca2+ concentrations thought to be derived from inositol 1,4,5-trisphosphate-sensitive and -insensitive intracellular stores. Whereas the importance of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores has been evaluated, the identity and role of inositol 1,4,5-trisphosphate-insensitive stores are poorly understood. To explore the role of the ryanodine-sensitive Ca2+ store, we first used reverse transcription-polymerase chain reaction to identify transcripts of the ryanodine receptor in eggs and determined that transcripts for the type 2 and 3 receptor were present. Immunoprecipitation of radioiodinated egg extracts with an antibody that recognizes both type 2 and 3 receptors detected specifically a band of Mr = 520,000. Immunolocalization of the receptor(s) using laser-scanning confocal microscopy revealed that the receptor(s) was uniformly distributed in the cortex of the germinal vesicle-intact oocyte, but became asymmetrically localized to the cortex in a region apposed to the meiotic spindle in the metaphase II-arrested egg; this asymmetrical localization developed by metaphase I. The role of the ryanodine receptor in mouse egg activation was examined by determining the effects of microinjected ryanodine or cyclic ADP ribose on endpoints of egg activation in either uninseminated or inseminated eggs. Ryanodine induced the conversion of the zona pellucida glycoprotein ZP2 to its postfertilization form ZP2f in a biphasic concentration-dependent manner; nanomolar concentrations stimulated this conversion, whereas micromolar concentrations had no stimulatory effect. Cyclic ADP ribose also promoted the ZP2 conversion, but with a hyperbolic concentration dependence. Neither of these compounds induced cell cycle resumption. Inhibiting the inositol 1,4,5-trisphosphate-sensitive Ca2+ store did not inhibit the ryanodine-induced ZP2 conversion and, reciprocally, inhibiting the ryanodine-sensitive Ca2+ store did not inhibit the inositol 1,4,5-trisphosphate-induced ZP2 conversion. Last, treatment of eggs under conditions that would block the release of Ca2+ from the ryanodine-sensitive store had no effect on any event of egg activation following fertilization. Results of these experiments suggest that although ryanodine receptors are present and functional, release of Ca2+ from this store is not essential for sperm-induced egg activation.

Induction of Hippocampal LTD Requires Nitric-Oxide-Stimulated PKG Activity and Ca2+ Release From Cyclic ADP-Ribose-Sensitive Stores

1999 ◽  
Vol 82 (3) ◽  
pp. 1569-1576 ◽  
Author(s):  
Magali Reyes-Harde ◽  
Barry V. L. Potter ◽  
Antony Galione ◽  
Patric K. Stanton
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Ryanodine Receptors ◽  
Low Frequency ◽  
Calcium Stores ◽  
No Donor ◽  
Cyclic Adp Ribose ◽  
Dependent Form ◽  
Frequency Stimulation

Long-term depression (LTD) of synaptic transmission can be induced by several mechanisms, one thought to involve Ca2+-dependent activation of postsynaptic nitric oxide (NO) synthase and subsequent diffusion of NO to the presynaptic terminal. We used the stable NO donor S-nitroso- N-acetylpenicillamine (SNAP) to study the NO-dependent form of LTD at Schaffer collateral-CA1 synapses in vitro. SNAP (100 μM) enhanced the induction of LTD via a cascade that was blocked by the N-methyl-d-aspartate receptor antagonist d-2-amino-5-phosphonopentanoic acid (50 μM), NO guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (10 μM), and the PKG inhibitor KT5823 (1 μM). We further show that LTD induced by low-frequency stimulation in the absence of SNAP also is blocked by KT5823 or Rp-8-(4-chlorophenylthio)-guanosine 3′,5′-cyclic monophosphorothioate (10 μM), cyclic guanosine 3′,5′ monophosphate-dependent protein kinase (PKG) inhibitors with different mechanisms of action. Furthermore SNAP-facilitated LTD was blocked when release from intracellular calcium stores was inhibited by ryanodine (10 μM). Finally, two cell-permeant antagonists of the cyclic ADP-ribose binding site on ryanodine receptors also were able to block the induction of LTD. These results support a cascade for induction of homosynaptic, NO-dependent LTD involving activation of guanylyl cyclase, production of guanosine 3′,5′ cyclic monophosphate and subsequent PKG activation. This process has an additional requirement for release of Ca2+ from ryanodine-sensitive stores, perhaps dependent on the second-messenger cyclic ADP ribose.

scholarly journals Cd38/Adp-Ribosyl Cyclase

1999 ◽  
Vol 146 (5) ◽  
pp. 1161-1172 ◽  
Author(s):  
Li Sun ◽  
Olugbenga A. Adebanjo ◽  
Baljit S. Moonga ◽  
Susanne Corisdeo ◽  
Hindupur K. Anandatheerthavarada ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Mrna Expression ◽  
Ryanodine Receptors ◽  
Predicted Amino Acid Sequence ◽  
Cytoplasmic Staining ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose ◽  
Agonist Antibody ◽  
Osteoclast Function

The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD+ to cyclic ADP-ribose (cADPr). The latter gates Ca2+ release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library. The predicted amino acid sequence displayed 59, 59, and 50% similarity, respectively, to the mouse, rat, and human CD38. In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts, confirming CD38 mRNA expression. Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CD38 protein. The ADP-ribosyl cyclase activity of osteoclastic CD38 was next demonstrated by its ability to cyclize the NAD+ surrogate, NGD+, to its fluorescent derivative cGDP-ribose. We then examined the effects of CD38 on osteoclast function. CD38 activation by an agonist antibody (A10) in the presence of substrate (NAD+) triggered a cytosolic Ca2+ signal. Both ryanodine receptor modulators, ryanodine, and caffeine, markedly attenuated this cytosolic Ca2+ change. Furthermore, the anti-CD38 agonist antibody expectedly inhibited bone resorption in the pit assay and elevated interleukin-6 (IL-6) secretion. IL-6, in turn, enhanced CD38 mRNA expression. Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr.

Metabotropic glutamate receptor-mediated cyclic ADP ribose signalling

2015 ◽  
Vol 43 (3) ◽  
pp. 405-409 ◽  
Author(s):  
Aidan Kaar ◽  
Mark G. Rae
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Calcium Release ◽  
Metabotropic Glutamate Receptor ◽  
Ryanodine Receptors ◽  
Calcium Stores ◽  
Ip3 Receptors ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Cyclic Adp Ribose ◽  
Key Aspects

Group I metabotropic glutamate receptors (I-mGluRs) modulate numerous cellular functions such as specific membrane currents and neurotransmitter release linked to their ability to mobilize calcium from intracellular calcium stores. As such, most I-mGluR research to date has focused on the coupling of these receptors to phospholipase C (PLC)-dependent and inositol (1,4,5) trisphosphate (IP3)-mediated calcium release via activation of IP3 receptors located upon the sarco/endoplasmic reticulum. However, there are now numerous examples of PLC- and IP3-independent I-mGluR-evoked signals, which may instead be mediated by activation of ryanodine receptors (RyRs). A prime candidate for mediating this coupling between I-mGluR activation and RyR opening is cyclic ADP ribose (cADPR) and, indeed, several of these PLC-/IP3-independent I-mGluR-evoked calcium signals have now been shown to be mediated wholly or partly by cADPR-evoked activation of RyRs. The contribution of cADPR signalling to I-mGluR-mediated responses is relatively complex, dependent as it is on factors such as cell type, excitation state of the cell and location of I-mGluRs on the cell. However, these factors notwithstanding, I-mGluR-mediated cADPR signalling remains poorly characterized, with several key aspects yet to be fully elucidated such as (1) the range of stimuli which evoke cADPR production, (2) the specific molecular mechanism(s) coupling cADPR to RyR activation and (3) the contribution of cADPR-mediated responses to downstream outputs such as synaptic plasticity. Furthermore, it is possible that the cADPR pathway may play a role in diseases underpinned by dysregulated calcium homoeostasis such as Alzheimer's disease (AD).

Cyclic ADP ribose-mediated Ca2+ signaling in mediating endothelial nitric oxide production in bovine coronary arteries

2006 ◽  
Vol 290 (3) ◽  
pp. H1172-H1181 ◽  
Author(s):  
Guo Zhang ◽  
Eric G. Teggatz ◽  
Andrew Y. Zhang ◽  
Matthew J. Koeberl ◽  
Fan Yi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Arteries ◽  
Ryanodine Receptors ◽  
No Production ◽  
Signaling Mechanism ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca ◽  
A Cell ◽  
Endothelial Nitric Oxide

The present study tested the hypothesis that cyclic ADP ribose (cADPR) serves as a novel second messenger to mediate intracellular Ca2+ mobilization in coronary arterial endothelial cells (CAECs) and thereby contributes to endothelium-dependent vasodilation. In isolated and perfused small bovine coronary arteries, bradykinin (BK)-induced concentration-dependent vasodilation was significantly attenuated by 8-bromo-cADPR (a cell-permeable cADPR antagonist), ryanodine (an antagonist of ryanodine receptors), or nicotinamide (an ADP-ribosyl cyclase inhibitor). By in situ simultaneously fluorescent monitoring, Ca2+ transient and nitric oxide (NO) levels in the intact coronary arterial endothelium preparation, 8-bromo-cADPR (30 μM), ryanodine (50 μM), and nicotinamide (6 mM) substantially attenuated BK (1 μM)-induced increase in intracellular [Ca2+] by 78%, 80%, and 74%, respectively, whereas these compounds significantly blocked BK-induced NO increase by about 80%, and inositol 1,4,5-trisphosphate receptor blockade with 2-aminethoxydiphenyl borate (50 μM) only blunted BK-induced Ca2+-NO signaling by about 30%. With the use of cADPR-cycling assay, it was found that inhibition of ADP-ribosyl cyclase by nicotinamide substantially blocked BK-induced intracellular cADPR production. Furthermore, HPLC analysis showed that the conversion rate of β-nicotinamide guanine dinucleotide into cyclic GDP ribose dramatically increased by stimulation with BK, which was blockable by nicotinamide. However, U-73122, a phospholipase C inhibitor, had no effect on this BK-induced increase in ADP-ribosyl cyclase activity for cADPR production. In conclusion, these results suggest that cADPR importantly contributes to BK- and A-23187-induced NO production and vasodilator response in coronary arteries through its Ca2+ signaling mechanism in CAECs.

Identification of phospholipase activity in Rhinella arenarum sperm extract capable of inducing oocyte activation

Zygote ◽  
2013 ◽  
Vol 22 (4) ◽  
pp. 483-495 ◽  
Author(s):  
Federico Bonilla ◽  
Carlos Minahk ◽  
María Teresa Ajmat ◽  
Graciela Sánchez Toranzo ◽  
Marta Inés Bühler
Keyword(s):  
Ryanodine Receptors ◽  
Cortical Granule ◽  
Oocyte Activation ◽  
Kinase C ◽  
Cyclic Adp Ribose ◽  
Sperm Extract ◽  
Rhinella Arenarum ◽  
Cortical Granule Exocytosis ◽  
Pronuclear Formation

SummaryEgg activation, which includes cortical granule exocytosis, resumption and completion of meiosis and pronuclear formation culminates in the first mitotic cleavage. However, the mechanism through which the fertilizing sperm induces this phenomenon is still controversial. We investigated the effect of the microinjection of homologous sperm soluble fractions obtained by fast protein liquid chromatography (FPLC) from reacted sperm (without acrosome) and non-reacted sperm on the activation of Rhinella arenarum oocytes matured in vitro. The FPLC-purified sperm fraction obtained from reacted or non-reacted sperm is able to induce oocyte activation when it is microinjected. This fraction has a 24 kDa protein and showed phospholipase C (PLC) activity in vitro, which was inhibited by D-609 but not by n-butanol or neomycin, suggesting that it is a PLC that is specific for phosphatidylcholine (PC-PLC). The assays conducted using inhibitors of inositol triphosphate (IP3) and ryanodine receptors (RyRs) indicate that the fraction with biological activity would act mainly through the cADPr (cyclic ADP ribose) pathway. Moreover, protein kinase C (PKC) inhibition blocks the activation produced by the same fraction. Immunocytochemical studies indicate that this PC-PLC can be found throughout the sperm head.

Hypoxia stimulates Ca2+ release from intracellular stores in astrocytes via cyclic ADP ribose-mediated activation of ryanodine receptors

Cell Calcium ◽  
2006 ◽  
Vol 39 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Parvinder K. Aley ◽  
Hilary J. Murray ◽  
John P. Boyle ◽  
Hugh A. Pearson ◽  
Chris Peers
Keyword(s):  
Ryanodine Receptors ◽  
Cyclic Adp Ribose
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