Activation of protein kinase C inhibits extraction of serotonin by perfused rat lung in situ

W. Weng, B. R. Pitt

Research output: Contribution to journalArticlepeer-review

Abstract

Pulmonary endothelial extraction (E) of serotonin (5-HT) is decreased after exposure to phorbol myristate acetate (PMA) in intact (D. Riggs, A.M. Havill, B.R. Pitt, and C.N. Gillis, J. Appl. Physiol. 64: 2508-2516, 1988.) or perfused (C.L. Myers and B.R. Pitt. J. Appl. Physiol. 65: 377-384, 1988.) lungs. Although the mechanism underlying this change is unclear, we hypothesized, based on studies in cultured pulmonary arterial endothelial cells [C.L. Myers, J.S. Lazo, and B.R. Pitt. Am. J. Physiol. 258 (Lung Cell. Mol. Physiol. 1): L253-L258, 1989] that activation of protein kinase C (PKC) by PMA inhibits this uptake process. Accordingly, we studied the ability of staurosporine, a potent inhibitor of PKC, to block the acute effect of PMA on E(5-HT) by rat lungs perfused at 10 ml/min with Krebs-bicarbonate with 3% albumin. Pulmonary E(5-HT) was measured by indicator-dilution techniques using 5-[3H]HT and [14C]dextran. Both PMA and mezerein (nonphorbol PKC activator) caused dose-dependent decreases in E(5-HT) and increases in perfusion pressure (Ppa). Staurosporine, alone, did not significantly affect either E(5-HT) or Ppa; however, staurosporine (100 nM) completely inhibited the effects of PMA (100 nM) on the above parameters. Papaverine, a nonspecific vasodilator, was able to partially inhibit the pressor response to PMA while not affecting the inhibition of E(5-HT) by PMA, suggesting that the effect on E(5-HT) was not secondary to vasoconstriction (and derecruitment). These data support the hypothesis that activation of PKC leads to prominent pulmonary vascular effects including vasoconstriction and inhibition of endothelial cell 5-HT uptake.

Original languageEnglish (US)
Pages (from-to)L289-L293
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume258
Issue number6 2-3
DOIs
StatePublished - 1990

Keywords

  • perfused lung
  • phorbol myristate acetate
  • pulmonary endothelium
  • serotonin
  • staurosporine

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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