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cADPR, a potent calcium-mobilizing intracellular messenger synthesized by ADP-ribosyl cyclases regulates openings of ryanodine receptors (RyR). Here we report that in the rat testis, a functional cADPR Ca2+ release system is essential for the contractile response of peritubular smooth muscle cells (PSMC) to endothelin (ET). We previously showed that this potent smooth muscle agonist elicits intracellular Ca2+ release in PSMC and seminiferous tubule contraction via activation of ETA and ETB receptors. ETB-R induces the mobilization of a thapsigargin-sensitive but IP3-independent intracellular Ca2+ pool. Stimulation of permeabilized PSMC with cADPR was found to elicit large Ca2+ releases blocked by either a selective antagonist of cADPR or a RyR blocker, but not by heparin. Western blotting and confocal fluorescence microscopy indicated the specific expression of type 2 RyR in perinuclear localization. ET was found to stimulate the activity of ADP-ribosyl cyclase. Microinjection of the selective cADPR antagonist 8NH2-cADPR completely abolished subsequent stimulation of Ca2+ signaling via ETA and ETB receptors. cADPR therefore appears to have an obligatory role for ETA-R and ETB-R-mediated calcium signaling in PSMC. However, ETB-R seem to be coupled exclusively to cADPR whereas ETA-R activation may be linked to IP3 and cADPR signaling pathways.

Original publication

DOI

10.1096/fj.01-0749com

Type

Journal article

Journal

FASEB J

Publication Date

05/2002

Volume

16

Pages

697 - 705

Keywords

ADP-ribosyl Cyclase, ADP-ribosyl Cyclase 1, Adenosine Diphosphate Ribose, Animals, Antigens, CD, Antigens, Differentiation, Blotting, Western, Boron Compounds, Calcium Channels, Calcium Signaling, Cell Membrane, Cells, Cultured, Culture Techniques, Cyclic ADP-Ribose, Endothelin-1, Endothelins, Fluorescent Dyes, Inositol 1,4,5-Trisphosphate Receptors, Male, Membrane Glycoproteins, Muscle Contraction, Muscle, Smooth, NAD+ Nucleosidase, Peptide Fragments, Rats, Receptor, Endothelin B, Receptors, Cytoplasmic and Nuclear, Receptors, Endothelin, Ryanodine, Ryanodine Receptor Calcium Release Channel, Seminiferous Tubules