ANALYSIS OF THE MECHANISMS UNDERLYING THE CONTRACTILE RESPONSE INDUCED BY THE HYDROALCOHOLIC EXTRACT OF PHYLLANTHUS URINARIA IN THE GUINEA-PIG URINARY-BLADDER IN-VITRO

The hydroalcoholic extract of Phyllanthus urinaria (Euphorbiaceae), su bstance P and substance P methyl ester all caused graded contractions in the guinea-pig urinary bladder. Responses to hydroalcoholic extract and substance P were markedly inhibited in calcium-free Krebs solutio n, this effect being reversed by reintroduction of calcium in the medi um. The contraction in response to hydroalcoholic extract was unaffect ed by atropine, propranolol, prazosin, yohimbine, tetrodotoxin, w-cono toxin, nicardipine, HOE 140, guanethidine, staurosporine, phorbol este r or indomethacin, excluding the involvement of nervous mediated respo nses, or action via cholinergic, adrenergic, kinins, cyclo-oxygenase m etabolites, protein kinase C or activation oft or N-type calcium chann els. The selective NK1 tachykinin antagonist (FK 888), but not NK2 (SR 48968) antagonized substance P-induced contraction, but both drugs fa iled to effect Phyllanthus urinaria-induced contraction. Prolonged des ensitization of guinea pig urinary bladder with capsaicin (10 mu M) or preincubation of guinea-pig urinary bladder with capsazepine did not affect contraction caused by hydroalcoholic extract. Ruthenium red alm ost completely abolished capsaicin-induced contraction, but had no eff ect on hydroalcoholic extract-mediated contraction. Substance P and th e hydroalcoholic extract caused marked potentiation of the twitch resp onse in the preparations field stimulated. The facilitatory effect of substance P, but not that of hydroalcoholic extract, was prevented by the NK1 (PK 888), but not by NK2 (SR 48968) antagonist. We concluded t hat contraction induced by hydroalcoholic extract of Phyllanthus urina ria in the guinea pig urinary bladder involves direct action on smooth muscle and relies on the mobilization of extracellular calcium influx unrelated to activation of L- and N-type calcium channels or activati on of protein kinase C mechanisms. In addition contraction caused by t he hydroalcoholic extract of Phyllanthus urinaria in guinea-pig urinar y bladder does not involve the activation of tachykinin or vanilloid r eceptors.