Enhancement of 5-hydroxytryptamine3A receptor function by phorbol 12-myristate, 13-acetate is mediated by protein kinase C and tyrosine kinase activity

S. J. Coultrap, Tina K. Machu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The effects of phorbol 12-myristate, 13-acetate (PMA) on 5-hydroxytryptamine (5-HT)-evoked ion currents in the mouse 5-HT3A receptor were examined. Perfusion with PMA caused a concentration dependent potentiation of 5-HT mediated currents and increased both potency and efficacy of 5-HT at the 5-HT3A receptor expressed in Xenopus oocytes. Enhancement of receptor function was partially blocked by injection of oocytes with PKCI, the peptide inhibitor of protein kinase C (PKC). Mutation of all 12 intracellular serine and threonine residues to alanine was without effect on PMA-induced potentiation of 5-HT elicited currents. Mutation of tyrosine 458 in the 5-HT3A receptor lacking intracellular serines and threonines reduced the PMA-induced potentiation of 5-HT evoked currents by ∼-55%. In contrast, mutation of tyrosine 458 in the wild-type receptor did not alter PMA-induced enhancement. The tyrosine kinase inhibitor, lavendustin A, reduced the enhancement of 5-HT3A receptor mediated currents by PMA in the mutant 5-HT3A receptor containing no intracellular serine or threonine residues, but not in the wild-type receptor. Thus, the role of intracellular serines and threonines is redundant with that of tyrosine, suggesting that these two components act through a similar pathway in response to PMA treatment.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalReceptors and Channels
Volume8
Issue number2
DOIs
StatePublished - 29 Aug 2002

Keywords

  • 5-HT receptor
  • Phorbol ester
  • Phosphorylation
  • Protein kinase C
  • Serotonin

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