In this study we evaluated the anti-adrenergic response elicited by ayanin, a flavonoid compound ... more In this study we evaluated the anti-adrenergic response elicited by ayanin, a flavonoid compound isolated from Croton schiedeanus Schlecht, in the pithed rat, and the inhibitory effect of NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and its acute toxicity profile in mice. In pithed rats ayanin (5 - 50 mg/kg i. v.) caused a dose-dependent decrease in the pressor and chronotropic responses induced by intravenous noradrenaline administration (0.25 microg/kg). This anti-adrenergic response was completely abolished by prior treatment with L-NAME (10 mg/kg i.v ) and the inhibitory effect of L-NAME was reversed after intravenous administration of L-arginine (100 mg/kg, i. v.). No lethal or major toxic effects were observed in mice receiving i. p. administration of ayanin up to a dose of 500 mg/kg. Our findings confirm that ayanin exerts protective cardiovascular effects against the increase in blood pressure and heart rate mainly through a mechanism that depends on the NO/cyclic guanosine monophosphate (cGMP) pathway without acute toxic effects. These results suggest that extracts of Croton schiedeanus, the native south American plant from which ayanin was isolated, might be beneficial in cardiovascular disease.
In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uter... more In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uterine muscular contractions induced by acetylcholine and calcium. The antagonism is more efficient for the alkaloid coclaurine which is even stronger than papaverine. The pA2 values obtained with each of the four alkaloids for both agents, acetylcholine and calcium, respectively, were as follows: reticuline (5.35 and 4.81), norarmepavine (5.55 and 4.09), coclaurine (7.42 and 6.91), papaverine (5.32 and 6.23). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the four alkaloids. The reduction is greater for the tonic phase, with the following IC50 values: reticuline 474 microM, norarmepavine 101 microM, coclaurine 68.9 microM, and papaverine 14.3 microM. The antispasmodic activity of the three alkaloids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, an intracellular effect, or both.
The bronchodilatory effect of the butanolic extract of A. caerulescens subsp. gallica on anaesthe... more The bronchodilatory effect of the butanolic extract of A. caerulescens subsp. gallica on anaesthetized guinea-pigs and in vitro preparations of guinea pig trachea was studied. The extract antagonized the bronchoconstrictory action of histamine and acetylcholine. The concentration response curves obtained in the in vitro preparations were shifted to the right in the presence of beta-adrenergic blocking agents: propranolol or ICI 118.551.
In vitro, the peracetates of penstemonoside, aucubin and catalpol, iridoids isolated from Parentu... more In vitro, the peracetates of penstemonoside, aucubin and catalpol, iridoids isolated from Parentucellia latifolia, antagonize the uterine muscular contractions induced by acetylcholine and calcium, in a similar way to papaverine. The antagonism is non-competitive against acetylcholine (pD2' values: 5.60 for the peracetates of penstemonoside, 5.74 for aucubin, 5.59 for catalpol, and 5.32 for papaverine) and competitive against calcium (pA2 values: 6.60 for the peracetates of penstemonoside, 6.34 for aucubin, 6.48 for catalpol, and 6.23 for papaverine). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the three iridoids. The reduction is similar for both phases. The antispasmodic activity of the three iridoids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, intracellular or both.
Naunyn-schmiedebergs Archives of Pharmacology, 2002
In the present study we attempted to characterise the responses and receptors involved in the eff... more In the present study we attempted to characterise the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT, serotonin) in in situ autoperfused rat hindquarters. Intra-arterial administration of the lowest doses of 5-HT used (0.12–12.5 ng/kg) induced vasodilator responses, whereas the highest doses (25–1000 ng/kg) produced vasoconstriction. The vasodilator effect was inhibited by methiothepin (a non-specific 5-HT1,2,5,6,7 receptor antagonist) and by a 5-HT1D/1B receptor antagonist, i.e., 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanolol (BRL 15572), but not by ritanserin (a selective 5-HT2 receptor antagonist), 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f] indole (SB 206553, a selective 5-HT2B/2C receptor antagonist) or mesulergine (a non-specific serotonergic antagonist that shows affinity to the 5-HT7 receptor). This vasodilator effect was mimicked by administration of a selective 5-HT1 receptor agonist – 5-carboxamidotryptamine (5-CT) – and by 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-1H-indol-3-yl]ethanamine (L-694,247, a selective 5-HT1D/1B receptor agonist). Methiothepin, but not mesulergine, inhibited 5-CT-induced vasodilatation and the selective 5-HT1D/1B receptor antagonist (BRL 15572) inhibited the vasodilator action induced by L-694,247. The vasoconstrictor effect of 5-HT was significantly decreased by methiothepin, ritanserin and SB 206553, and was mimicked by α-methyl-5-HT (a selective 5-HT2 receptor agonist) but not by administration of BW 723C86, a selective 5HT2B receptor agonist. Ritanserin, SB 206553 and spiperone (a non-specific 5-HT1/2A receptor antagonist) inhibited the α-methyl-5HT-induced vasoconstriction. Our data suggest that the vasodilator response induced by 5-HT in autoperfused rat hindquarters is mainly mediated by 5-HT1D/1B receptors, whereas the vasoconstrictor effect is mainly due to the activation of 5-HT2A receptors.
1A study was made of the effects of 5-carboxamidotryptamine (5-CT) on pressor responses induced i... more 1A study was made of the effects of 5-carboxamidotryptamine (5-CT) on pressor responses induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Sympathetic stimulation (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. Intravenous infusion of 5-CT at doses of 0.01, 0.1 and 1 μg kg−1 min−1 reduced the pressor effects obtained by electrical stimulation. The inhibitory effect of 5-CT was significantly more pronounced at lower frequencies of stimulation. In the present study we characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-CT.2The inhibition induced by 0.01 μg kg−1 min−1 of 5-CT on sympathetically-induced pressor responses was partially blocked after i.v. treatment with methiothepin (10 μg kg−1), WAY-100,635 (100 μg kg−1) or GR127935T (250 μg kg−1), but was not affected by cyanopindolol (100 μg kg−1).3The selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT1B/1D receptor agonists sumatriptan and L-694,247 inhibited the pressor response, whereas the 5-HT1B receptor agonists CGS-12066B and CP-93,129 and the 5-HT2C receptor agonist m-CPP did not modify the pressor symapthetic responses.4The selective 5-HT1A receptor antagonist WAY-100,635 (100 μg kg−1) blocked the inhibition induced by 8-OH-DPAT and the selective 5-HT1B/1D receptor antagonist GR127935T (250 μg kg−1) abolished the inhibition induced either by L-694,247 or sumatriptan.5None of the 5-HT receptor agonists used in our experiments modified the pressor responses induced by exogenous noradrenaline (NA).6These results suggest that the presynaptic inhibitory action of 5-CT on the electrically-induced pressor response is mediated by both r-5-HT1D and 5-HT1A receptors.A study was made of the effects of 5-carboxamidotryptamine (5-CT) on pressor responses induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Sympathetic stimulation (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. Intravenous infusion of 5-CT at doses of 0.01, 0.1 and 1 μg kg−1 min−1 reduced the pressor effects obtained by electrical stimulation. The inhibitory effect of 5-CT was significantly more pronounced at lower frequencies of stimulation. In the present study we characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-CT.The inhibition induced by 0.01 μg kg−1 min−1 of 5-CT on sympathetically-induced pressor responses was partially blocked after i.v. treatment with methiothepin (10 μg kg−1), WAY-100,635 (100 μg kg−1) or GR127935T (250 μg kg−1), but was not affected by cyanopindolol (100 μg kg−1).The selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT1B/1D receptor agonists sumatriptan and L-694,247 inhibited the pressor response, whereas the 5-HT1B receptor agonists CGS-12066B and CP-93,129 and the 5-HT2C receptor agonist m-CPP did not modify the pressor symapthetic responses.The selective 5-HT1A receptor antagonist WAY-100,635 (100 μg kg−1) blocked the inhibition induced by 8-OH-DPAT and the selective 5-HT1B/1D receptor antagonist GR127935T (250 μg kg−1) abolished the inhibition induced either by L-694,247 or sumatriptan.None of the 5-HT receptor agonists used in our experiments modified the pressor responses induced by exogenous noradrenaline (NA).These results suggest that the presynaptic inhibitory action of 5-CT on the electrically-induced pressor response is mediated by both r-5-HT1D and 5-HT1A receptors.British Journal of Pharmacology (1998) 123, 1205–1213; doi:10.1038/sj.bjp.0701714
In this study we evaluated the anti-adrenergic response elicited by ayanin, a flavonoid compound ... more In this study we evaluated the anti-adrenergic response elicited by ayanin, a flavonoid compound isolated from Croton schiedeanus Schlecht, in the pithed rat, and the inhibitory effect of NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and its acute toxicity profile in mice. In pithed rats ayanin (5 - 50 mg/kg i. v.) caused a dose-dependent decrease in the pressor and chronotropic responses induced by intravenous noradrenaline administration (0.25 microg/kg). This anti-adrenergic response was completely abolished by prior treatment with L-NAME (10 mg/kg i.v ) and the inhibitory effect of L-NAME was reversed after intravenous administration of L-arginine (100 mg/kg, i. v.). No lethal or major toxic effects were observed in mice receiving i. p. administration of ayanin up to a dose of 500 mg/kg. Our findings confirm that ayanin exerts protective cardiovascular effects against the increase in blood pressure and heart rate mainly through a mechanism that depends on the NO/cyclic guanosine monophosphate (cGMP) pathway without acute toxic effects. These results suggest that extracts of Croton schiedeanus, the native south American plant from which ayanin was isolated, might be beneficial in cardiovascular disease.
In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uter... more In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uterine muscular contractions induced by acetylcholine and calcium. The antagonism is more efficient for the alkaloid coclaurine which is even stronger than papaverine. The pA2 values obtained with each of the four alkaloids for both agents, acetylcholine and calcium, respectively, were as follows: reticuline (5.35 and 4.81), norarmepavine (5.55 and 4.09), coclaurine (7.42 and 6.91), papaverine (5.32 and 6.23). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the four alkaloids. The reduction is greater for the tonic phase, with the following IC50 values: reticuline 474 microM, norarmepavine 101 microM, coclaurine 68.9 microM, and papaverine 14.3 microM. The antispasmodic activity of the three alkaloids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, an intracellular effect, or both.
The bronchodilatory effect of the butanolic extract of A. caerulescens subsp. gallica on anaesthe... more The bronchodilatory effect of the butanolic extract of A. caerulescens subsp. gallica on anaesthetized guinea-pigs and in vitro preparations of guinea pig trachea was studied. The extract antagonized the bronchoconstrictory action of histamine and acetylcholine. The concentration response curves obtained in the in vitro preparations were shifted to the right in the presence of beta-adrenergic blocking agents: propranolol or ICI 118.551.
In vitro, the peracetates of penstemonoside, aucubin and catalpol, iridoids isolated from Parentu... more In vitro, the peracetates of penstemonoside, aucubin and catalpol, iridoids isolated from Parentucellia latifolia, antagonize the uterine muscular contractions induced by acetylcholine and calcium, in a similar way to papaverine. The antagonism is non-competitive against acetylcholine (pD2' values: 5.60 for the peracetates of penstemonoside, 5.74 for aucubin, 5.59 for catalpol, and 5.32 for papaverine) and competitive against calcium (pA2 values: 6.60 for the peracetates of penstemonoside, 6.34 for aucubin, 6.48 for catalpol, and 6.23 for papaverine). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the three iridoids. The reduction is similar for both phases. The antispasmodic activity of the three iridoids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, intracellular or both.
Naunyn-schmiedebergs Archives of Pharmacology, 2002
In the present study we attempted to characterise the responses and receptors involved in the eff... more In the present study we attempted to characterise the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT, serotonin) in in situ autoperfused rat hindquarters. Intra-arterial administration of the lowest doses of 5-HT used (0.12–12.5 ng/kg) induced vasodilator responses, whereas the highest doses (25–1000 ng/kg) produced vasoconstriction. The vasodilator effect was inhibited by methiothepin (a non-specific 5-HT1,2,5,6,7 receptor antagonist) and by a 5-HT1D/1B receptor antagonist, i.e., 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanolol (BRL 15572), but not by ritanserin (a selective 5-HT2 receptor antagonist), 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f] indole (SB 206553, a selective 5-HT2B/2C receptor antagonist) or mesulergine (a non-specific serotonergic antagonist that shows affinity to the 5-HT7 receptor). This vasodilator effect was mimicked by administration of a selective 5-HT1 receptor agonist – 5-carboxamidotryptamine (5-CT) – and by 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-1H-indol-3-yl]ethanamine (L-694,247, a selective 5-HT1D/1B receptor agonist). Methiothepin, but not mesulergine, inhibited 5-CT-induced vasodilatation and the selective 5-HT1D/1B receptor antagonist (BRL 15572) inhibited the vasodilator action induced by L-694,247. The vasoconstrictor effect of 5-HT was significantly decreased by methiothepin, ritanserin and SB 206553, and was mimicked by α-methyl-5-HT (a selective 5-HT2 receptor agonist) but not by administration of BW 723C86, a selective 5HT2B receptor agonist. Ritanserin, SB 206553 and spiperone (a non-specific 5-HT1/2A receptor antagonist) inhibited the α-methyl-5HT-induced vasoconstriction. Our data suggest that the vasodilator response induced by 5-HT in autoperfused rat hindquarters is mainly mediated by 5-HT1D/1B receptors, whereas the vasoconstrictor effect is mainly due to the activation of 5-HT2A receptors.
1A study was made of the effects of 5-carboxamidotryptamine (5-CT) on pressor responses induced i... more 1A study was made of the effects of 5-carboxamidotryptamine (5-CT) on pressor responses induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Sympathetic stimulation (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. Intravenous infusion of 5-CT at doses of 0.01, 0.1 and 1 μg kg−1 min−1 reduced the pressor effects obtained by electrical stimulation. The inhibitory effect of 5-CT was significantly more pronounced at lower frequencies of stimulation. In the present study we characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-CT.2The inhibition induced by 0.01 μg kg−1 min−1 of 5-CT on sympathetically-induced pressor responses was partially blocked after i.v. treatment with methiothepin (10 μg kg−1), WAY-100,635 (100 μg kg−1) or GR127935T (250 μg kg−1), but was not affected by cyanopindolol (100 μg kg−1).3The selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT1B/1D receptor agonists sumatriptan and L-694,247 inhibited the pressor response, whereas the 5-HT1B receptor agonists CGS-12066B and CP-93,129 and the 5-HT2C receptor agonist m-CPP did not modify the pressor symapthetic responses.4The selective 5-HT1A receptor antagonist WAY-100,635 (100 μg kg−1) blocked the inhibition induced by 8-OH-DPAT and the selective 5-HT1B/1D receptor antagonist GR127935T (250 μg kg−1) abolished the inhibition induced either by L-694,247 or sumatriptan.5None of the 5-HT receptor agonists used in our experiments modified the pressor responses induced by exogenous noradrenaline (NA).6These results suggest that the presynaptic inhibitory action of 5-CT on the electrically-induced pressor response is mediated by both r-5-HT1D and 5-HT1A receptors.A study was made of the effects of 5-carboxamidotryptamine (5-CT) on pressor responses induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Sympathetic stimulation (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. Intravenous infusion of 5-CT at doses of 0.01, 0.1 and 1 μg kg−1 min−1 reduced the pressor effects obtained by electrical stimulation. The inhibitory effect of 5-CT was significantly more pronounced at lower frequencies of stimulation. In the present study we characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-CT.The inhibition induced by 0.01 μg kg−1 min−1 of 5-CT on sympathetically-induced pressor responses was partially blocked after i.v. treatment with methiothepin (10 μg kg−1), WAY-100,635 (100 μg kg−1) or GR127935T (250 μg kg−1), but was not affected by cyanopindolol (100 μg kg−1).The selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT1B/1D receptor agonists sumatriptan and L-694,247 inhibited the pressor response, whereas the 5-HT1B receptor agonists CGS-12066B and CP-93,129 and the 5-HT2C receptor agonist m-CPP did not modify the pressor symapthetic responses.The selective 5-HT1A receptor antagonist WAY-100,635 (100 μg kg−1) blocked the inhibition induced by 8-OH-DPAT and the selective 5-HT1B/1D receptor antagonist GR127935T (250 μg kg−1) abolished the inhibition induced either by L-694,247 or sumatriptan.None of the 5-HT receptor agonists used in our experiments modified the pressor responses induced by exogenous noradrenaline (NA).These results suggest that the presynaptic inhibitory action of 5-CT on the electrically-induced pressor response is mediated by both r-5-HT1D and 5-HT1A receptors.British Journal of Pharmacology (1998) 123, 1205–1213; doi:10.1038/sj.bjp.0701714
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