| 20357193 |
Lee YC, Chang HH, Liu CH, Chen MF, Chen PY, Kuo JS, Lee TJ: Methyl Palmitate: A Potent Vasodilator Released in the Retina. . Invest Ophthalmol Vis Sci. 2010 Mar 31.
Purpose: To determine if 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 pharmacological characteristics of RRF and PAME were compared. Results: We demonstrated that the retina upon 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, since 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 hr, suggesting that both are heat stable. Exogenous PAME concentration-dependently induced aortic relaxation with EC50 of 0.82+/-0.75 pmol/L. The aortic relaxations induced by RRF and exogenous PAME were inhibited by 4-aminopyridine (4-AP, 2 mmol/L) and tetraethylammonium (TEA, 10 mmol/L), but were not affected by TEA at 1 mmol/L or 3 mmol/L, glibenclamide (3 mumol/L), or iberiotoxin (100 nmol/L). The vasodilator activity of Krebs' solution containing RRF or exogenous PAME was greatly attenuated following hexane extraction. Conclusions: RRF and PAME share similar biochemical properties and react similarly to all pharmacological 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. |
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