Neurochemical Research

, Volume 15, Issue 11, pp 1109–1114 | Cite as

Alteration of the GTP-dependent inhibitory pathway of rat striatal adenylate cyclase by phorbol esters

  • Maria C. Olianas
  • Pierluigi Onali
Original Articles
Accepted:

Abstract

In membranes of rat striatum, phorbol 12-myristate 13-acetate (PMA), a potent activator of Ca2+/phospholipid-dependent protein kinase, enhanced adenylate cyclase activity by counteracting the inhibition elicited by GTP. Exposure to pertussis toxin caused a similar alteration of the GTP-regulation of the enzyme activity and largely prevented the PMA effects. PMA treatment increased by threefold the GTP requirement of acetylcholine-induced inhibition of adenylate cyclase activity but did not affect the GTP-dependence of the enzyme stimulation by dopamine. The hydrolysis of GTP by membrane-bound high affinity GTPase was significantly inhibited by PMA (IC 50 10 nM) in a Ca2+-dependent manner. Like PMA, phorbol 12, 13-dibutyrate inhibited the GTPase activity, whereas the biologically inactive 4-β phorbol 13-acetate and 4-β phorbol were without effect. These results suggest that activation of Ca2+/phospholipid-dependent protein kinase by PMA stimulates adenylate cyclase activity by impairing the activity of the GTP-dependent inhibitory protein, possibly through a reduction of the GTP-GDP exchange.

Key Words

Phorbol esters adenylate cyclase GTP hydrolysis rat striatum 
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Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Maria C. Olianas
    • 1
  • Pierluigi Onali
    • 1
  1. 1.Department of NeurosciencesUniversity of CagliariCagliariItaly

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