The Relaxant Effect of Extract of Phyllanthus urinaria in the Guinea-pig Isolated Trachea. Evidence for Involvement of ATP-sensitive Potassium Channels (original) (raw)
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… : The Vascular System, 1996
The hydroalcoholic extract (HE) of stems, leaves and roots from P. urinaria (Eu. phorbiaceae) (1-3000 l~g/ml), caused graded contraction in guinea pig trachea (GPT), being more effective in preparations without epithelium. 2. Response to HE was slightly affected by tetrodotoxin (0.3 ~M) and nicardipine (1 ~M), but was unaffected by w-conotoxin, atropine, mepyramine or staurosporine (all 1 ~M). Indomethacin (3 ~M) greatly inhibited HE contraction, but MK 571 (leukotriene D4 and E 4 antagonist) caused partial inhibition; L-655,240 (thromboxane A2 antagonist) and WEB 2086 (PAF antagonist) (all 1 ttM) were ineffective. 3. Response to HE was markedly inhibited in a Ca2+-free solution and was partially affected in GPT desensitized to capsaicin (10 I~M). 4. Capsazepine (capsaicin antagonist, 3 I~M) antagonized the contraction from capsaicin, leaving the response to HE unaffected. In contrast, ruthenium red (an ionic channel antagonist coupled to vanilloid receptors of capsaicin) (0.1-3 ~M) caused graded and equipotent noncompetitive inhibition of HE-and capsaicin-induced contractions, but had no effect on carbachol-and prostaglandin Ez-mediated responses. 5. FK 888 and SR 48968 (NKI and NK2 receptor antagonists, respectively) (both 1 ~M) antagonized, through a competitive mechanism, the contraction from SP and [~-alaS]NKA(4.10) respectively, but antagonized, through a noncompetitive mechanism, HE-mediated contraction. 6. We concluded that contraction to HE in GPT is modulated by the epithelium, depends on the release of a cyclo-oxygenase metabolite, and relies largely upon an extracellular Ca 2+ influx that is highly sensitive to ruthenium red, but is insensitive to L and N-type of voltage-sensitive Ca z+ channel antagonists. In addition, NKt and NK2 tachykinins, but not vanilloid receptors, play an important role in mediating its response. OEN PHARMAC 27;5:795-802, 1996.
Journal of Smooth Muscle Research, 2013
Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of natural products with therapeutic potential. A possible interaction between diterpene and the Ca 2+-calmodulin complex was eliminated as chlorpromazine (10-6 M), a calmodulin inhibitor, did not significantly alter the diterpeneinduced relaxation (pD 2 = 4.38 ± 0.07 and 4.25 ± 0.07; mean ± S.E.M., n=5). Trachylobane-318 showed a higher relaxant potency when the trachea was contracted by 18 mM KCl than it did with 60 mM KCl (pD 2 = 4.90 ± 0.25 and 3.88 ± 0.01, n=5), suggesting the possible activation of K + channels. This was confirmed, as in the presence of 10 mM TEA + (a non-selective K + channel blocker), diterpene relaxation potency was significantly reduced (pD 2 = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K + channel subtypes K ATP , K V , SK Ca and BK Ca seem to be modulated positively by trachylobane-318 (pD 2 = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the K ir subtype channel (pD 2 = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD 2 = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10-5 M trachylobane-318 (pD 2 = 4.46 ± 0.08, n=5). Thus, at a functional level, trachylobane-318 seems to relax the guinea-pig trachea by positive modulation of K + channels, particularly the K ATP , K V , SK Ca and BK Ca subtypes.
African Journal of Traditional, Complementary and Alternative Medicines, 2005
The present study was designed to investigate the blocking of calcium by the hydroalcoholic extract of Tapinanthus dodoneifolius (Tapidod), "in vitro", on rat trachea. To evaluate this effect, the contractile activity of tracheal chains from Wistar Kyoto rats was isometrically recorded. On the isolated tracheal rings the extract produced the following effects: (a) a reduction of the contraction obtained by BaCl 2 , (b) a bronchorelaxing action, on strips precontracted by KCl, which was not influenced by TEA (3x10-3 M), (c) a concentrationdependent decrease of the spasm evoked by calcium chloride (CaCl 2) in K-rich Ca-free physiological salt solution + 2+ , before and after intracellular calcium depletion (d), an inhibitory effect on contraction induced by acetylcholine in Ca-free Krebs-Heinseleit solution supplemented with 2+ EDTA (5x10-4 M). It is concluded that: 1. The activation of the potassium channels does not play a significant role in the relaxant effect of Tapidod. 2. The antispasmodic property of Tapidod seems to be mediated by the blockade of intracellular Ca 2+ release. 3. Most likely an inhibition of the intracellular Ca 2+-regulating proteins is involved.
Pharmaceutical Biology, 2016
Context: Agastache mexicana ssp. mexicana (Kunth) Lint & Epling (Lamiaceae), popularly known as 'toronjil morado', is used in Mexican traditional medicine for the treatment of several diseases such as hypertension, anxiety and respiratory disorders. Objective: This study investigates the relaxant action mechanism of A. mexicana ssp. mexicana essential oil (AMEO) in guinea-pig isolated trachea model. Materials and method: AMEO was analyzed by GC/MS. The relaxant effect of AMEO (5-50 lg/mL) was tested in guinea-pig trachea pre-contracted with carbachol (3 Â 10 À 6 M) or histamine (3 Â 10 À 5 M) in the presence or absence of glibenclamide (10 À 5 M), propranolol (3 Â 10 À 6 M) or 2 0 ,5 0-dideoxyadenosine (10 À 5 M). The antagonist effect of AMEO (10-300 lg/mL) against contractions elicited by carbachol (10 À 15-10 À 3 M), histamine (10 À 15-10 À 3 M) or calcium (10-300 lg/mL) was evaluated. Results: Essential oil composition was estragole, D-limonene and linalyl anthranilate. AMEO relaxed the carbachol (EC 50 ¼ 18.25 ± 1.03 lg/mL) and histamine (EC 50 ¼ 13.3 ± 1.02 lg/mL)-induced contractions. The relaxant effect of AMEO was not modified by the presence of propranolol, glibenclamide or 2 0 ,5 0-dideoxyadenosine, suggesting that effect of AMEO is not related to b 2-adrenergic receptors, ATP-sensitive potassium channels or adenylate cyclase activation. AMEO was more potent to antagonize histamine (pA 2 0 ¼ À1.507 ± 0.122) than carbachol (pA 2 0 ¼ À2.180 ± 0.357). Also, AMEO antagonized the calcium chloride-induced contractions. Conclusion: The results suggest that relaxant effect of AMEO might be due to blockade of calcium influx in guinea-pig trachea smooth muscle. It is possible that estragole and D-limonene could contribute majority in the relaxant effect of AMEO.
Phytotherapy Research, 2003
In previous studies, the relaxant and anticholinergic (functional antagonism), histamine(H 1) inhibitory, and xanthine-like activity effect of Carum copticum have been demonstrated on guinea pig tracheal chains. To investigate the effective component(s) of this plant, responsible for the observed bronchodilatory effect, fractionation of the essential oil from Carum copticum was carried out and the relaxant effects of different fractions were examined in this study. The bronchodilatory effect of different fractions of essential oil from Carum copticum and theophylline in comparison with ethanol was examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 µ µ µ µ µM methacholine in two different conditions including: non-incubated tissues (group 2) and incubated tissues with 1 µ µ µ µ µM propranolol and 1 µ µ µ µ µM chlorpheniramine (group 3). In addition the relaxant effect of carvacrol was also examined on precontracted tracheal chains of guinea pig by 10 µ µ µ µ µM methacholine (group 4), (for each group, n = = = = = 5). In group 1 experiments, only theophylline and fraction 2 showed significant relaxant effect compared to that of ethanol. Fraction 2 and 3 of essential oil from carum copticum showed potent and volume (concentration) dependent relaxant effects comparable to that of theophylline in groups 2 and 3 experiments. The relaxant effects of different volumes of these two fractions were significantly higher than that of ethanol (p < < < < < 0.05 to p < < < < < 0.002). The volumes of fraction 1 showed relatively small relaxant effects in groups 2 and 3 experiments which were not significantly different from that of ethanol. However, the relaxant effect of different volumes of fractions 2 and 3 obtained in group 2 experiments were not significantly different from those of group 3 experiments. The volumes of fraction 4 did not show any relaxant effects. In addition volumes of carvacrol also showed comparable relaxant effect with those of fraction 2 and theophylline which was significantly greater than that of ethanol. These results indicate that the relaxant effect of essential oil from carum copticum is mainly due to its fraction 2 which is presumably carvacrol and to lesser extent due to fraction 3, and their relaxant effects are not due to anticholinergic or β β β β β-adrenegic stimulatory effects.
Journal of ethnopharmacology, 2018
Lippia origanoides H.B.K. is an aromatic species used in folk medicine to treat respiratory diseases, including asthma. The aim of this work was to evaluate the relaxing potential and mechanism of action of the L. origanoides (LOO) essential oil in isolated guinea-pig trachea. Leaves from L. origanoides were collected at experimental fields under organic cultivation, at the Forest Garden of Universidade Estadual de Feira de Santana. Essential oil was extracted by hydrodistillation, analyzed by GC/FID and GC/MS and the volatile constituents were identified. Spasmolytic activity and relaxant mechanism of LOO were assayed in isolated guinea-pig trachea contracted with histamine, carbachol or hyperpolarizing KCl. Chemical analysis revealed the presence of carvacrol (53.89%) as major constituent. LOO relaxed isolated guinea-pig trachea pre-contracted with KCl 60 mM [EC = 30.02 μg/mL], histamine 1 µM [EC = 9.28 μg/mL] or carbachol 1 µM [EC = 51.80 μg/mL]. The pre-incubation of glibenclami...
Journal of Ethnopharmacology, 2007
We investigated the mechanisms of action of Gnaphalium liebmannii which is used as a folk medicine in México for treating various respiratory diseases such as gripe, fever, asthma, cough, cold, bronchitis, expectorating, and bronchial affections. The tension changes of guinea pig tracheal segments were isometrically recorder on a polygraph. Hexane extract of Gnaphalium liebmannii was the most active relaxant extract (IC 30 = 54.23 ± 19.79 g/mL with 99.5 ± 3.2 % of relaxation), followed by dichloromethane extract (IC 30 = 120.22 ± 5.27 g/mL) and methanol extract (IC 30 = 190.25 ± 30.02 g/mL). Hexane extract produced a parallel rightward shift of the concentration-response curve of carbachol in a competitive manner (pA 2 = −2.4), but did not modify the concentration-response curves for histamine. The relaxant effect of hexane extract of Gnaphalium liebmannii was unaffected by the presence of propranolol (3 × 10 −6 M) or glibenclamide (10 M). However hexane extract produced a leftward shifts of the concentration-response curve of forskolin (10 −8 to 10 −3 M), nitroprusside (10 −10 to 10 −6 M), isoproterenol (3 × 10 −10 to 3 × 10 −5 M) and aminophylline (10 −11 to 10 −2 M). The above results suggest that Gnaphalium liebmannii induce relaxation of the tracheal muscle, probably via phosphodiesterase inhibition. The bronchodilator effect of Gnaphalium liebmannii might explain in part their traditional use as anti-asthmatic remedy.
Fundamental & Clinical Pharmacology, 2005
The relaxant effects of the Taxodium mucronatum Ten leaf hexane extract on intestinal and tracheal smooth muscle were evaluated in vitro by testing spontaneous contractions of rabbit jejunum and agonist-induced contractions of guinea pig ileum and rat trachea. The extract produced a concentration-dependent relaxation of the spontaneous contractions of rabbit jejunum (EC 50 : 4.9 ± ± ± ± 0.5 µg/ml) that was equipotent to papaverine. Following incubation of guinea pig ileum with the extract, the concentration-response curves to acetylcholine, histamine, 5-hydroxytryptamine and Ca 2+ were displaced to the right and the maximum response was significantly reduced. K + -induced contraction of the ileal tissue was completely abolished with 31.6 µg/ml of the extract. In rat tracheal rings, the extract inhibited both 1 µM carbachol (EC 50 : 33.9 ± ± ± ± 2.5 µg/ml) and 60 mM K + (EC 50 : 20.6 ± ± ± ± 1.1 µg/ml)-induced contractions. It also caused the concentration-response to Ca 2+ curves to shift to the right in a noncompetitive manner. These results demonstrate a non-specific relaxant effect that could be mediated through inhibition of calcium influx via both voltage-and receptor-gated calcium channels. The relaxant activity induced by this extract provides a rational basis for the traditional use of T. mucronatum to treat disorders of the gastrointestinal and respiratory tracts.