The type 2 ryanodine receptor of neurosecretory PC12 cells is activated by cyclic ADP-ribose. Role of the nitric oxide/cGMP pathway

Emilio Clementi, Maria Riccio, Clara Sciorati, Giuseppe Nisticò, Jacopo Meldolesi

Research output: Contribution to journalArticlepeer-review

Abstract

Of two neurosecretory PC12 cell clones that respond to NO donors and 8- bromo-cGMP with similar increases in cADP-ribose and that possess molecularly similar Ca2+ stores, only one (clone 16A) expresses the type 2 ryanodine receptor, whereas the other (clone 27) is devoid of ryanodine receptors. In PC12-16A cells, activation of the NO/cGMP pathway induced slow [Ca2+](i) responses, sustained by release from Ca2+ stores. In contrast, PC12-27 cells were insensitive to NO donors. Likewise, in PC12-16A cells preincubated with NO donors, Ca2+ stores were partially depleted, as revealed by a test with thapsigargin, whereas those in clone 27 were unchanged. The NO-induced Ca2+ release was increased synergistically by caffeine, and the corresponding store depletion was magnified by ryanodine. The specificity for the NO/cGMP pathway was confirmed by the effects of two blockers of cGMP- dependent protein kinase I, while the role of cADP-ribose was demonstrated by the effects of its antagonist, 8-amino-cADP-ribose, administered to permeabilized cells. These results demonstrate in neurosecretory cells a ryanodine receptor activation pathway similar to that known in sea urchin oocytes. The signaling events described here could be of great physiological importance, especially in the nervous system.

Original languageEnglish
Pages (from-to)17739-17745
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number30
DOIs
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Biochemistry

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