Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02427 (Atropine)
 3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prokinetic benzamides (e.g., cisapride) enhance gastrointestinal motility and transit. In vitro studies on the guinea pig ileum suggest that their effect is mediated via serotonergic 5-hydroxytryptamine (5-HT4) receptors, resulting in a facilitation of cholinergic neurotransmission. However, most in vivo studies have been performed on the canine stomach. Therefore, our aim was to determine whether the findings obtained on the guinea pig ileum can be extrapolated to another species and another organ. Does a benzamide facilitate cholinergic neutrotransmission on strips of the canine stomach in vitro? If so, does the benzamide exert its effect via a serotonergic 5-HT4 mechanism? Longitudinal muscle strips with adhering myenteric plexus were isolated from the canine stomach and were electrically stimulated at submaximal frequencies resulting in a mean contractile response of 16 +/- 7% of the response to methacholine (10(-6) M). Atropine and tetrodotoxin (both 3 x 10(-7) M) abolished the contractile responses, whereas hexamethonium (10(-4) M) had no effect. Cisapride (3 x 10(-7) M) enhanced the contractile responses from 14 to 70% (59 +/- 5% increase). 5-HT (3 x 10(-7) M) similarly enhanced the responses from 12 to 72% (58 +/- 5% increase). Cisapride induced a sustained enhancement throughout the duration of the experiment; in contrast, the effect of 5-HT subsided in about 90 min. Single-concentration administration of cisapride (10(-8)-10(-6) M) and 5-HT (10(-9)-3 x 10(-7) M) resulted in EC50 values of 1.0 (0.8-1.4) x 10(-7) M for cisapride and 1.3 (0.8-2.1) x 10(-8) M for 5-HT. Methiothepin and methysergide (both 3 x 10(-7) M; 5-HT1-receptor antagonists), ketanserin and LY 53857 (both 3 x 10(-7) M; 5-HT2-receptor antagonists), granisetron (3 x 10(-7) M; 5-HT3-receptor antagonist) or ICS 205-930 (3 x 10(-7) M; 5-HT3-receptor antagonist and in addition 5-HT4-receptor antagonist at 3 x 10(-6) M) did not reduce the responses to both cisapride and 5-HT. 1-(1-Naphthalenyl)piperazine (10(-6) M; 5-HT-receptor antagonist in the rat gastric fundus) significantly reduced the increase by 5-HT (24 +/- 7%; 7-31%) but had no effect on the cisapride (3 x 10(-7) M)-induced increase (69 +/- 4%; 8-77%).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cisapride and 5-hydroxytryptamine enhance motility in the canine antrum via separate pathways, not involving 5-hydroxytryptamine1,2,3,4 receptors. 809 33

The presence of serotonin (5-HT) in the chicken gastrointestinal tract has been previously reported, but its motor effects have been poorly described. The aims of this work were: A) to define the effects of 5-HT on chicken longitudinal ileum; B) to explore the mechanisms by which such effects occur and C) to identify the subtype(s) of 5-HT-ergic receptors implicated. The motor responses to 5-HT were assayed in vitro using ileal strips taken from male White Leghorn chickens 7-9 week old. 5-HT elicited ileal contraction (EC50 9.6 x 10(-8) M), which was markedly decreased in the presence of tetrodotoxin (TTX). Repeated exposure of the tissue to supramaximal concentrations of 5-HT did not however lead to desensitization. Atropine (10(-6) M), ketanserin (10(-5) M), methysergide (10(-5) M) and methiothepine (10(-6) M) attenuated the response to 5-HT. Ketanserin was an effective inhibitor of the residual response to 5-HT obtained even in the presence of TTX. Several serotonergic agonists were assayed to further analyse the type of receptors involved in the response to 5-HT. 5-methoxytryptamine (5-MOT), a mixed 5-HT1, 5-HT2 and 5-HT4 agonist, reproduced all the effects of 5-HT. 8-OH-DPAT, a selective 5-HT1A agonist, trifluoromethylphenylpiperazine, a mixed 5-HT1B/C agonist, and m-chlorophenylbiguanide, a 5-HT3 agonist, did not induce any consistent contractile effects. Sumatriptan, a 5-HT1D agonist, exerted a slight agonistic effect which was blocked by methiothepine and decreased by TTX but not by atropine. Cisapride, a 5-HT4 partial agonist in mammals, decreased the effects of both 5-HT and 5-MOT. These results indicate that chicken ileum contains 5-HT1 receptors similar to the 5-HT1D mammalian subtype but not the 5-HT1A, 5-HT1B, 5-HT1C or 5-HT3 subtypes. 5-HT2 receptors are also present and would appear to be located on smooth muscle.
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PMID:Receptors implicated in the actions of serotonin on chicken ileum longitudinal smooth muscle. 846 35

The effects evoked by 5-hydroxytryptamine (5-HT; serotonin) on forestomach myoelectric activity were investigated in conscious sheep. Myoelectric signals were recorded with electrodes chronically implanted in the reticulum, rumen (dorsal sac) and omasal body, and were analysed by a computer-based method. The 5-HT receptors and the neuronal pathways involved in these actions were studied. The intravenous (i.v.) infusion of 5-HT (8 micrograms kg-1 min-1 for 5 min) evoked an inhibition of activity of the whole forestomach. Methiothepin, injected i.v. at 0.1 mg kg-1, inhibited rumen secondary contractions and omasum activity. However, forestomach activity remained unchanged after the administration of 0.2 mg kg-1 of ketanserin, ondansetron, tropisetron, GR-113808, phentolamine, propranolol, domperidone and naloxone. Atropine (0.2 mg kg-1), hexamethonium (2 mg kg-1) or haloperidol (0.1 mg kg-1) abolished rumen secondary cycles and inhibited omasum activity. In addition, atropine also suppressed primary cycles. GR-113808 blocked all 5-HT-induced effects. Furthermore, atropine or hexamethonium prevented the 5-HT-evoked inhibition of reticulorumen primary cycles. In contrast, the remaining antagonists did not alter the 5-HT-evoked forestomach hypomotility. In conclusion, 5-HT induces inhibition of forestomach myoelectric activity through 5-HT4 receptors, these actions being mediated by cholinergic neural pathways involving muscarinic and nicotinic receptors. However, adrenergic, dopaminergic or opiate pathways are not implicated.
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PMID:5-Hydroxytryptamine induces forestomach hypomotility in sheep through 5-HT4 receptors. 888 77

This study examined effects of 5-methoxytryptamine (5-MOT), an agonist at 5-HT4 and 5-HT2B receptors, on the contractile response and acetylcholine release in rat stomach fundus strips. 5-MOT (10(-9)-10(-5) M) produced a concentration-dependent increase in the contraction, while it evoked acetylcholine release in a 'bell-shaped' concentration-dependent manner. Atropine reduced 5-MOT (10(-8)-10(-6) M)-induced contractions, but it had little effect on the contractions evoked by higher concentrations. 5-MOT-induced contraction and acetylcholine release were inhibited by SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-[diethylamino] ethyl ester), a 5-HT4 receptor antagonist. In the presence of atropine, both SDZ 205-557 and yohimbine, a 5-HT2B receptor antagonist, inhibited the contraction. In the presence of tetrodotoxin, the contraction was inhibited by yohimbine, but not by SDZ 205-557. These results suggest that the contractile action of 5-MOT in rat stomach fundus involves atropine-sensitive and atropine-resistant components. The sensitive contraction appears to be mediated through 5-HT4 receptors located on cholinergic neurons, whereas the resistant contraction is mediated through 5-HT4 receptors located on non-cholinergic neurons and through 5-HT2B receptors.
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PMID:Characterization of the contractile response induced by 5-methoxytryptamine in rat stomach fundus strips. 901 31

We investigated the mechanism of 5-hydroxytryptamine (5-HT)-induced contraction in the longitudinal muscle of isolated distal ileum from ferrets, piglets and rats. 5-HT and 5-methoxytryptamine concentration-dependently contracted the ileum of ferrets, piglets and rats. 2-Methyl-5-HT and m-chlorophenylbiguanide concentration-dependently contracted the ferret ileum, whereas they had no effect in piglets and rats. In ferrets, the 5-HT-induced contraction was inhibited by methysergide and by ramosetron, but not by ketanserin or GR113808. Atropine and tetrodotoxin suppressed contractions elicited by 5-HT, 2-methyl-5-HT and m-chlorophenylbiguanide in ferrets, but not that elicited by 5-methoxytryptamine. In piglets, 5-HT-induced contraction was inhibited by methysergide and by tetrodotoxin, but not by ketanserin, ramosetron, GR113808 or atropine. In rats, 5-HT-induced contraction was inhibited by methysergide and by ketanserin, but not by ramosetron or tetrodotoxin. In contrast, GR113808 enhanced contractions elicited by 5-HT or 5-methoxytryptamine. These results suggest that 5-HT-induced contraction in ferrets is mediated via 5-HT1 receptors on the muscle and by release of acetylcholine via 5-HT3 receptors. In piglets, 5-HT-induced contraction appears to be mediated by release of neurotransmitters other than acetylcholine via 5-HT1 receptors. 5-HT-induced contraction in rats is evoked via 5-HT1 and 5-HT2 receptors on the muscle. Furthermore, 5-HT4 receptors may participate in the relaxation elicited by 5-HT in rats.
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PMID:Species differences in the 5-hydroxytryptamine-induced contraction in the isolated distal ileum. 926 87

The function of 5-hydroxytryptamine (5-HT) receptors, especially the 5-HT4 receptor, in the urinary bladder were examined in preparations isolated from the guinea pig by in vitro receptor autoradiography and determinations of mechanical activity and acetylcholine (ACh) release. Specific [125I]SB207710 binding sites were detected evenly throughout the urinary bladder. 5-HT (3 x 10(-8)-10(-4) M) caused contractions of strips of the urinary bladder, in a concentration dependent manner. Ketanserin antagonized the 5-HT-induced contractions, while granisetron and SB204070 antagonized the contractions induced by high concentrations of 5-HT. Atropine inhibited the contractions induced by high concentrations of 5-HT. Ketanserin prevented the 5-HT-induced contractions in the presence of atropine, but granisetron and SB204070 did not affect the contractions under such a condition. 5-HT enhanced the electrically-stimulated (5 Hz, 0.5 ms) outflow of [3H]acetylcholine from strips preloaded with [3H]choline, and the enhancement was antagonized by granisetron and SB204070. Thus, the contractile response to 5-HT was mediated by activations of 5-HT2, 5-HT3 and 5-HT4 receptors. The 5-HT2 receptor may be a property of high affinity to 5-HT and located on the smooth muscle cells. The 5-HT4 as well as 5-HT3 receptor may be a property of low affinity to 5-HT and located on the cholinergic neurons.
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PMID:5-Hydroxytryptamine receptors, especially the 5-HT4 receptor, in guinea pig urinary bladder. 1223 12

Spontaneous contractions of the intestine are thought to play an important role in the gastrointestinal motility, including peristalsis. In the present study, we investigated mechanisms for regulation of the frequency of spontaneous contractions, using longitudinal muscle strips in rat distal colon. Atropine significantly decreased the frequency of spontaneous contractions, indicating that neuromuscular transmission via muscarinic receptors increases the frequency of spontaneous contractions. SB-204070, 5-HT4 receptor antagonist also significantly decreased the frequency of spontaneous contractions, indicating that the activation of 5-HT4 receptors also increases the frequency of spontaneous contractions. In conclusion, it is suggested that muscarinic and 5-HT4 receptors participate in the regulation of the frequency of spontaneous contractions in the longitudinal muscle in rat distal colon, and that the frequency of spontaneous contraction is controlled by the enteric neurons.
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PMID:Muscarinic and 5-HT4 receptors participate in the regulation of the frequency of spontaneous contractions of the longitudinal muscle in rat distal colon. 1615 33

We examined the effects of intravenous administration of purified arc-discharge single-walled carbon nanotubes (SWCNTs) on rabbit ileum to establish the possibility of using these SWCNTs as cell markers or drug carriers for the treatment of intestinal diseases. The SWCNT purification process eliminated carbonaceous impurities and decreased the amount of metals. SWCNTs increased the contractile responses induced by KCl, acetylcholine (ACh), and serotonin (5-HT) in rabbit ileum. Verapamil, apamin, glibenclamide, quinine and charybdotoxin reduced the contractile responses induced by ACh and 5-HT in ileum from rabbits treated with SWCNTs, indicating that voltage-dependent Ca2+ channels and small, intermediate, and large-conductance Ca(2+)-activated, ATP-sensitive, and voltage-dependent K+ channels are involved in these effects. Atropine and hexamethonium reduced the ACh response, indicating that muscarinic and nicotinic receptors are involved in this effect. Ondansetron and GR 113808 reduced the 5-HT response, indicating that serotonin 5-HT3 and 5-HT4 receptors are involved in this effect. SWCNTs increased the malondialdehyde plus 4-hydroxyalkenals and carbonyl levels in rabbit plasma and ileum, indicating that SWCNTs produce oxidative stress. SWCNTs did not produce relevant histological changes or modify the levels of the inflammatory mediators iNOS and COX-2 in the ileum. In conclusion, this study demonstrates that the intravenous administration of SWCNTs can evoke oxidative stress and affect contractility in rabbit ileum. These effects could reduce the possibility of using the arc-discharge SWCNTs as cell markers or drug carriers to treat intestinal diseases.
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PMID:Single-walled carbon nanotubes (SWCNTs) enhance KCl-, acetylcholine-, and serotonin-induced contractions and evoke oxidative stress on rabbit ileum. 2473 Feb 48