The mechanisms underlying the relaxant effect of methyl and ethyl gallates in the guinea pig trachea in vitro: contribution of potassium channels

Abstract

The relaxant response and the possible contribution of K+ channels to the relaxation caused by both methyl and ethyl gallates, two compounds isolated from the Brazilian medicinal plant Phyllanthus urinaria, were investigated in the guinea pig trachea in vitro. Both methyl and ethyl gallate (0.01-30 microM) caused graded and complete relaxation of the guinea pig trachea without epithelium, pre-contracted by histamine, with mean EC50 values of 1.8 (1.2-2.2) microM and 0.7 (0.6-0.8) microM, respectively, and Emax of both 100+/-0%. Response to ethyl, but not methyl gallate, was significantly shifted to the right, with no change in the maximum effect when the epithelium was removed. The increase in K+ concentration in the medium to 80 mM completely abolished the relaxant response caused by both methyl and ethyl gallate. In addition, tetraethylammonium (10 mM) reduced by 50+/-6% and 43+/-4% the relaxation caused by methyl and ethyl gallates. In contrast, glibenclamide (3 microM) shifted (by about two- and fourfold) the concentration-response curves for both methyl and ethyl gallates, with no changes in the maximum effect. Charybdotoxin (100 nM), but not apamin (100 nM), significantly blocked by 54+/-5% and 59+/-4% the relaxation of both methyl and ethyl gallates. In contrast, SQ 22536 (10 microM; a selective adenylyl cyclase inhibitor), methylene blue (10 microM) or ODQ (1 microM; a guanylyl cyclase inhibitor) did not significantly affect the relaxant response caused by either of the compounds. These results provide evidence that the relaxation caused by both methyl and ethyl gallates in the guinea pig trachea in vitro may involve the activation of large-conductance Ca2+-activated K+ channels, and, to a lesser extent, ATP-sensitive K+ channels. Such results extend our previous observations and are consistent with the notion that methyl and ethyl gallates are mainly responsible for the relaxant action previously demonstrated in the extract of this plant.

Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat

“…However, charybdotoxin, a potent inhibitor of large-conductance Ca 2 + -activated potassium (LK Ca ) channels was unable to modify isosteviol vasodilatation. Usually, the concentration of charybdotoxin used to impair the large-conductance Ca 2 + -activated potassium (LK Ca ) channels was about 10 À 8 M (Paulino et al, 1999). In the present study, the concentration of charybdotoxin used was 10-fold higher than that previously used, indicating that an action of isosteviol on LK Ca channels in aortic rings can be ruled out.…”

The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation

“…This discrepancy might be attributable to differences in Pn dose, which was much lower in the present study than used previously [9]. However, Pn and other plants belonging to the genus Phyllanthus have antispasmodic and relaxant effects on many contractile tissues, including trachea, ileum, uterus and aorta [11][12][13]. These effects might also occur in urethral smooth muscle and contribute to the elimination of smaller calculi.…”

Evaluation of Larvicidal andin Vitro. Antiparasitic Activities of Plants in a Biodiversity Plot in the Altos de Campana National Park, Panama

“…Ethyl gallate and methyl gallate have been reported to possess other biological activities such as antioxidant effect on free-radical scavenging (Op de Beck et al, 2003) and relaxant effect in guinea-pig trachea in vitro by activation of large conductance Ca 2þ activated K þ channels (Paulino et al, 1999). The only report on the chemistry of the genus Talisia is about the isolation of isolectins from T. escualenta (Freire et al, 2001).…”