Terpinen-4-ol: mechanisms of relaxation on rabbit duodenum

Abstract

The effect of terpinen-4-ol was studied on rabbit duodenum in-vitro. Terpinen-4-ol induced relaxation of the basal tonus (IC50 170.2 (95% confidence interval, 175–204) μm) with a maximal relaxant response of 180.4 ± 3.9% (n = 6) of the contraction induced by 60 mm [K+]. The maximal relaxation induced in control conditions was not affected (P>0.05) by pretreatment of the tissues with phentolamine (50 μm) or propranolol (10 μm), Ng nitro-l-arginine methyl ester (L-NAME; 1 mm), 1H-(1,2,4)-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 100 μm), hexamethonium (1 mm), tetrodotoxin (1 μm), the mixture charybdotoxin-apamin (1 μm), glibenclamide (10 μm), 4-aminopyridine (10 μm) or tetraethylammonium (100 μm). In addition, terpinen-4-ol completely relaxed tissues precontracted with 60 mm [K+] solutions (IC50 325.9 (245.1–433.1) μm) and also blocked (IC50 154.7 (117.7–191.7) μm) the phasic component of this contraction. At a concentration of 195 and 650 μm it reduced by 41.3 ± 3.4% and 75.4 ± 3.1%, respectively the maximal contractile response to Ca2+ in depolarized duodenum. Terpinen-4-ol completely blocked the component of carbachol-induced contraction, which was resistent to nifedipine (100 μm) pretreatment or to a Ca2+-free solution. These data show that terpinen-4-ol relaxes intestinal smooth muscle and suggest that this effect is myogenic in nature and depends on calcium antagonism.