A pivotal role for cADPR-mediated Ca 2+ signaling: Regulation of endothelin-induced contraction in peritubular smooth muscle cells

Fortunata Barone, Armando A. Genazzani, Antonio Conti, Grant C. Churchill, Fioretta Palombi, Elio Ziparo, Vincenzo Sorrentino, Antony Galione, Antonio Filippini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)697-705
Number of pages9
JournalFASEB Journal
Volume16
Issue number7
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • ADP-ribosyl cyclase
  • Calcium signaling
  • Ryanodine receptors
  • Seminiferous tubule

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