Second-messenger generation in PC12 cells. Interactions between cyclic AMP and Ca2+ signals

G. Gatti, L. Madeddu, A. Pandiella, T. Pozzan, J. Meldolesi

Research output: Contribution to journalArticle

Abstract

Changes in cyclic AMP concentrations were studied in intact PC12 pheochromocytoma cells exposed to a variety of treatments. A marked increase was triggered by N-(L-2-phenylisopropyl)adenosine, the activator of an adenosine receptor, whereas a decrease (observed even after phosphodiesterase blockade) was induced by carbachol, working through a muscarinic receptor inhibited by the selective muscarinic blocker pirenzepine, only at high concentration (K(i) 450 nM). A decrease in cyclic AMP was also induced by clonidine, an α2-adrenergic-receptor agonist. Both the α2-adrenergic and the muscarinic inhibitions were prevented by pretreatment of the cells with pertussis toxin, and were unaffected by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. The latter drug caused a decrease in the resting cyclic AMP concentrations, and a potentiation of the increase induced by adenosine-receptor activation. Except for clonidine, all these treatments were found to be effective in both growing PC12 cells and, although to a smaller degree, in cells that had stopped growing and had acquired a neuron-like phenotype after prolonged treatment with nerve growth factor (NGF). Neither forskolin (a direct activator of adenylate cyclase) nor the activation of adenosine and α-adrenergic receptors was able to modify the resting cytosolic Ca2+ concentration [Ca2+](i) in PC12 cells. Likewise, the K+-induced [Ca2+](i) transients were unchanged after these treatments, whereas the transients induced by carbachol through the activation of a muscarinic receptor higly sensitive to pirenzepine were moderately potentiated by forskolin (and, to a lesser degree, by the adenosine analogue) and attenuated by clonidine. These results characterize in further detail the spectrum and the mutual interrelationships of the intracellular signals induced by receptor activation in PC12 cells, also as a function of the NGF-induced differentiation.

Original languageEnglish
Pages (from-to)753-760
Number of pages8
JournalBiochemical Journal
Volume255
Issue number3
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Second-messenger generation in PC12 cells. Interactions between cyclic AMP and Ca2+ signals'. Together they form a unique fingerprint.

  • Cite this

    Gatti, G., Madeddu, L., Pandiella, A., Pozzan, T., & Meldolesi, J. (1988). Second-messenger generation in PC12 cells. Interactions between cyclic AMP and Ca2+ signals. Biochemical Journal, 255(3), 753-760.