MECHANISMS INVOLVED IN THE CONTRACTILE RESPONSES INDUCED BY THE HYDROALCOHOLIC EXTRACT OF PHYLLANTHUS-URINARIA ON THE GUINEA-PIG ISOLATED TRACHEA - EVIDENCE FOR PARTICIPATION OF TACHYKININS AND INFLUX OF EXTRACELLULAR CA2-RED( SENSITIVE TO RUTHENIUM)

1. The hydroalcoholic extract (HE) of stems, leaves and roots from P. urinaria (Euphorbiaceae) (1-3000 mu g/ml), caused graded contraction i n guinea pig trachea (GPT), being more effective in preparations witho ut epithelium. 2. Response to HE was slightly affected by tetrodotoxin (0.3 mu M) and nicardipine (1 (LM)1 but was unaffected by w-conotoxin , atropine, mepyramine or staurosporine (all 1 mu M). Indomethacin (3 mu M) greatly inhibited HE contraction, but MK 571 (leukotriene D-4 an d E(4) antagonist) caused partial inhibition; L-655,240 (thromboxane A z antagonist) and WEB 2086 (PAF antagonist) (all 1 mu M) were ineffect ive. 3. Response to HE was markedly inhibited in a Ca2+-free solution and was partially affected in GPT desensitized to capsaicin (10 mu M). 4. Capsazepine (capsaicin antagonist, 3 mu M) antagonized the contrac tion from capsaicin, leaving the response to HE unaffected. In contras t, ruthenium red (an ionic channel antagonist coupled to vanilloid rec eptors of capsaicin) (0.13 mu M) caused graded and equipotent noncompe titive inhibition of HE- and capsaicin-induced contractions, but had n o effect on carbachol- and prostaglandin E(2)-mediated responses. 5. F K 888 and SR 48968 (NK1 and NK2 receptor antagonists, respectively) (b oth 1 mu M) antagonized, through a competitive mechanism, the contract ion from SP and [beta-ala(8)]NKA(4-10) respectively, but antagonized, through a noncompetitive mechanism, HE-mediated contraction. 6. We con cluded that contraction to HE in GPT is modulated by the epithelium, d epends on the release of a cyclo-oxygenase metabolite, and relies larg ely upon an extracellular Ca2+ influx that is highly sensitive to ruth enium red, but is insensitive to L and N-type of voltage-sensitive Ca2 + channel antagonists. In addition, NK1 and NK2 tachykinins, but not v anilloid receptors, play an important role in mediating its response.