THE RELAXANT EFFECT OF EXTRACT OF PHYLLANTHUS-URINARIA IN THE GUINEA-PIG ISOLATED TRACHEA - EVIDENCE FOR INVOLVEMENT OF ATP-SENSITIVE POTASSIUM CHANNELS

This study analyses the relaxation induced by the hydroalcoholic extra ct of stems, leaves and roots from Phyllanthus urinaria (Euphorbiaceae ) in the guinea-pig trachea (GPT) pre-contracted by carbachol. The hyd roalcoholic extract of P. urinaria (0.1-10 mg mL(-1)) caused a graded relaxation in GPT with or without epithelium, with mean EC50 values of 1.94 (1.41-2.67) and 2.00 (1.47-2.78) mg mL(-1) and E(max) of 717 mg (+/- 16) and 627 mg (+/- 12), respectively. The relaxation in response to hydroalcoholic extract, like that to cromakalim (EC50 3.57 (2.75-4 .64 mu M) in GPT without epithelium, was fully abolished in the presen ce of high KCl concentrations (80 mM), and was significantly attenuate d by tetraethylammonium (10 or 30 mM) or glibenclamide (0.1 or 3 mu M) . However, the relaxation caused by the hydroalcoholic extract was una ffected by apamin (0.1 or 1.0 mu M), nitro-L-arginine (L-NOARG, 100 mu M), methylene blue (10 mu M) or by calcitonin gene-related peptide (C GRP) (8-37) (a CGRP antagonist, 0.1 mu M). Both propranolol (1 or 3 mu M) and [D-p-Cl-Phe(6),Leu(17)]VIP (a vasoactive intestinal peptide (V IP) receptor antagonist, 0.1 mu M) produced a significant displacement to the right (about 2-fold) of the relaxation response to hydroalcoho lic extract of P. urinaria. Thus, the present results indicate that th e ATP-activated potassium channels sensitive to glibenclamide, but not the small conductance calcium-activated potassium channels sensitive to apamin, largely contribute to the relaxation effect of the hydroalc oholic extract of P. urinaria in GPT. In addition, both beta(2) and VI P-mediated responses seem to account, at least in part, for the relaxa tion effect of the hydroalcoholic extract, as its relaxant response wa s partially attenuated by both propranolol and VIP receptor antagonist .