Existence of rolipram‐sensitive phosphodiesterase in rat megakaryocyte

Norio Akaike, Hisayuki Uneyama, Kazuyoshi Kawa, Yoshiro Yamashita

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7 Citations (Scopus)

Abstract

The effect of rolipram (ME3176) on ADP‐ and IP3‐induced repetitive IK(Ca) in rat megakaryocyte was investigated by use of the nystatin perforated patch and conventional whole‐cell patch‐clamp techniques. The ADP‐induced IK(Ca) was depressed by treatment with rolipram in a concentration‐dependent manner. The inhibition by rolipram disappeared after treatment with a cyclic nucleotide‐dependent protein kinase inhibitor, H‐8. The inhibition of IK(Ca) was also observed in the presence of cyclic AMP accumulating agents such as forskolin and isobutylmethylxanthine (IBMX). Rolipram enhanced the inhibitory action of forskolin, suggesting that rolipram facilitates the accumulation of cyclic AMP by blocking its breakdown. Similar results was obtained with adenosine, an endogenous adenylate cyclase activator. Intracellular application of inositol trisphosphate (IP3) induced repetitive IK(Ca) in megakaryocytes. The induced IK(Ca) was also inhibited by rolipram and by other cyclic AMP accumulating agents. It was concluded that megakaryocytes possess rolipram‐sensitive phosphodiesterase (PDE), which was not detected in platelets, but plays a distinct modulatory role in megakaryocytes for generating ADP‐induced IK(Ca). 1993 British Pharmacological Society

Original languageEnglish
Pages (from-to)1020-1023
Number of pages4
JournalBritish Journal of Pharmacology
Volume109
Issue number4
DOIs
Publication statusPublished - 1993 Aug

Keywords

  • Rolipram
  • calcium
  • cyclic AMP
  • nystatin perforated patch recording
  • phosphodiesterase
  • rat megakaryocyte

ASJC Scopus subject areas

  • Pharmacology

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