Methyl palmitate: a potent vasodilator released in the retina

Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4746-53. doi: 10.1167/iovs.09-5132. Epub 2010 Mar 31.


Purpose: To determine whether palmitic acid methyl ester (PAME) or methyl palmitate is the retina-derived relaxing factor (RRF).

Methods: A superfusion bioassay cascade technique was used with rat isolated retina as donor tissue and rat aortic ring as detector tissue. The superfusate was analyzed with gas chromatography/mass spectrometry (GC/MS). The biochemical and pharmacologic characteristics of RRF and PAME were compared.

Results: The authors demonstrated that the retina on superfusion with Krebs solution spontaneously released RRF (indicated by aortic ring relaxation) and PAME (measured by GC/MS). The release of RRF and PAME was calcium dependent because the release was abolished when the retinas were superfused with calcium-free Krebs solution. Furthermore, aortic relaxations induced by RRF and PAME were not affected after heating their solutions at 70 degrees C for 1 hour, suggesting that both are heat stable. Exogenous PAME concentration dependently induced aortic relaxation with EC50 of 0.82+/-0.75 pM. The aortic relaxations induced by RRF and exogenous PAME were inhibited by 4-aminopyridine (2 mM) and tetraethylammonium (TEA, 10 mM) but were not affected by TEA at 1 mM or 3 mM, glibenclamide (3 microM), or iberiotoxin (100 nM). The vasodilator activity of Krebs solution containing RRF or exogenous PAME was greatly attenuated after hexane extraction.

Conclusions: RRF and PAME share similar biochemical properties and react similarly to all pharmacologic inhibitors examined. Both act primarily on the voltage-dependent K+ (Kv) channel of aortic smooth muscle cells, causing aortic relaxation. These results suggest that PAME is the hydrophobic RRF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Aorta / physiology*
  • Biological Assay
  • Calcium / metabolism
  • Calcium / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Hexanes
  • Isotonic Solutions / metabolism
  • Isotonic Solutions / pharmacology
  • Male
  • Miconazole / pharmacology
  • Nitroarginine / pharmacology
  • Palmitates / isolation & purification
  • Palmitates / metabolism*
  • Peptides / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Proadifen / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Retina / metabolism*
  • Retinal Vessels / physiology*
  • Solvents
  • Tetraethylammonium / pharmacology
  • Vasodilation / drug effects
  • Vasodilation / physiology*


  • Enzyme Inhibitors
  • Hexanes
  • Isotonic Solutions
  • Krebs-Ringer solution
  • Palmitates
  • Peptides
  • Potassium Channel Blockers
  • Solvents
  • Nitroarginine
  • Tetraethylammonium
  • iberiotoxin
  • Miconazole
  • Proadifen
  • 4-Aminopyridine
  • methyl palmitate
  • Calcium