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A pivotal role for cADPR‐mediated Ca 2+ signaling: regulation of endothelin‐induced contraction in peritubular smooth muscle cells
Author(s) -
Barone Fortunata,
Genazzani Armando A.,
Conti Antonio,
Churchill Grant C.,
Palombi Fioretta,
Ziparo Elio,
Sorrentino Vincenzo,
Galione Antony,
Filippini Antonio
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0749com
Subject(s) - ryanodine receptor , thapsigargin , intracellular , endocrinology , cyclic adp ribose , medicine , receptor , endothelin receptor , signal transduction , calcium in biology , microbiology and biotechnology , chemistry , microinjection , biology , biochemistry , cd38 , stem cell , cd34
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 Ca 2+ 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 Ca 2+ release in PSMC and seminiferous tubule contraction via activation of ETA and ETB receptors. ETB‐R induces the mobilization of a thapsigargin‐sensitive but IP 3 ‐independent intracellular Ca 2+ pool. Stimulation of permeabilized PSMC with cADPR was found to elicit large Ca 2+ 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 8NH 2 ‐cADPR completely abolished subsequent stimulation of Ca 2+ 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 IP 3 and cADPR signaling pathways.