Translocation and Activation of Protein Kinase C in Striatal Neurons in Primary Culture: Relationship to Phorbol Dibutyrate Actions on the Inositol Phosphate Generating System and Neurotransmitter Release

Samuel Weiss, John Ellis, Daniel D. Hendley, Robert H. Lenox

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Abstract: The actions of the tumor‐promoting phorbol ester phorbol dibutyrate were examined, under identical physiological conditions, on three distinct cellular processes in striatal neurons: the distribution of protein kinase C, the carbachol‐stimulated generation of [3H]inositol monophosphate, and the KCl‐evoked release of γ‐[3H]aminobutyric acid ([3H]GABA). Phorbol dibutyrate induced a rapid (complete in 5 min), dose‐dependent, entirely reversible (t0.5= 15 min) translocation of protein kinase C from cytosol to membrane. On longer exposure to phorbol dibutyrate, membrane‐associated protein kinase C returned toward the control level, and total cellular enzyme activity declined markedly. Phorbol dibutyrate also induced the dose‐dependent attenuation of carbachol‐stimulated [3H]inositol monophosphate production and potentiation of KCl‐evoked release of [3H]GABA. The translocation of protein kinase C and the potentiation of KCl‐evoked [3H]GABA release were both rapidly reversed following washout of phorbol dibutyrate. In addition, for both processes, the effect of a 1‐h exposure to phorbol dibutyrate was markedly less than that observed following a 5‐min exposure to the agent. In direct contrast, inhibition of carbachol‐stimulated [3H]inositol monophosphate production was not rapidly reversed following washout of phorbol dibutyrate and was actually more pronounced following a 1‐h exposure, compared with a 5‐min exposure. These findings indicate that some, but not all, of the actions of phorbol dibutyrate are closely associated with the translocation of protein kinase C in striatal neurons in primary culture.

Original languageEnglish (US)
Pages (from-to)530-536
Number of pages7
JournalJournal of Neurochemistry
Volume52
Issue number2
DOIs
StatePublished - Jan 1 1989

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Translocation and Activation of Protein Kinase C in Striatal Neurons in Primary Culture: Relationship to Phorbol Dibutyrate Actions on the Inositol Phosphate Generating System and Neurotransmitter Release'. Together they form a unique fingerprint.

Cite this