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Interactions between propofol and lipid mediator receptors: inhibition of lysophosphatidate signaling.

Publication ,  Journal Article
Rossi, MA; Chan, CK; Christensen, JD; DeGuzman, EJ; Durieux, ME
Published in: Anesth Analg
November 1996

As a highly lipophilic drug, propofol may interact with lipophilic domains in addition to its likely primary site of action on the gamma-aminobutyrateA) (GABA(A)) receptor. Likely candidates for such interaction are the G protein-coupled membrane receptors for lipid intercellular mediators. The phospholipid lysophosphatidate (LP) has attracted attention as such a signaling molecule. It has a variety of biological actions, including vasoconstriction. We therefore studied the interaction between propofol and the LP receptor. Intracellular Ca2+ release in response to LP was assessed by measuring C1- flux through Ca(2+)-activated C1- channels in Xenopus oocytes. The average charge movement in response to LP 10(-7)M was 2.0 +/- 0.2 microCoulombs. Propofol in Intralipid (0.01%) dose-dependently inhibited LP signaling (50% inhibitory concentration [IC50] 5.38 microM). Propofol 28 microM inhibited LP signaling by 81%. Intralipid (0.01%) was without effect. To ascertain that intracellular signaling pathways and the Ca(2+)-activated C1- channel were not affected by propofol, we tested the effects of propofol (5.6 microM) on currents induced by methylcholine (10(-7)M) in oocytes expressing the m1 muscarinic acetylcholine receptor. No inhibition was observed. As both receptors share the same intracellular signaling pathway, we conclude that clinically relevant concentrations of propofol most likely inhibit the LP receptor or its G protein. Inhibition of LP signaling may explain some of propofol's vasodilating actions.

Duke Scholars

Published In

Anesth Analg

DOI

ISSN

0003-2999

Publication Date

November 1996

Volume

83

Issue

5

Start / End Page

1090 / 1096

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Vasodilator Agents
  • Vasoconstrictor Agents
  • Signal Transduction
  • Receptors, Muscarinic
  • Receptors, Cell Surface
  • Propofol
  • Oocytes
  • Muscarinic Antagonists
  • Lysophospholipids
 

Citation

APA
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Rossi, M. A., Chan, C. K., Christensen, J. D., DeGuzman, E. J., & Durieux, M. E. (1996). Interactions between propofol and lipid mediator receptors: inhibition of lysophosphatidate signaling. Anesth Analg, 83(5), 1090–1096. https://doi.org/10.1097/00000539-199611000-00034
Rossi, M. A., C. K. Chan, J. D. Christensen, E. J. DeGuzman, and M. E. Durieux. “Interactions between propofol and lipid mediator receptors: inhibition of lysophosphatidate signaling.Anesth Analg 83, no. 5 (November 1996): 1090–96. https://doi.org/10.1097/00000539-199611000-00034.
Rossi MA, Chan CK, Christensen JD, DeGuzman EJ, Durieux ME. Interactions between propofol and lipid mediator receptors: inhibition of lysophosphatidate signaling. Anesth Analg. 1996 Nov;83(5):1090–6.
Rossi, M. A., et al. “Interactions between propofol and lipid mediator receptors: inhibition of lysophosphatidate signaling.Anesth Analg, vol. 83, no. 5, Nov. 1996, pp. 1090–96. Pubmed, doi:10.1097/00000539-199611000-00034.
Rossi MA, Chan CK, Christensen JD, DeGuzman EJ, Durieux ME. Interactions between propofol and lipid mediator receptors: inhibition of lysophosphatidate signaling. Anesth Analg. 1996 Nov;83(5):1090–1096.

Published In

Anesth Analg

DOI

ISSN

0003-2999

Publication Date

November 1996

Volume

83

Issue

5

Start / End Page

1090 / 1096

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Vasodilator Agents
  • Vasoconstrictor Agents
  • Signal Transduction
  • Receptors, Muscarinic
  • Receptors, Cell Surface
  • Propofol
  • Oocytes
  • Muscarinic Antagonists
  • Lysophospholipids