Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the influences of both PO2 and the presence of the endothelium on contractile responses of the human umbilical artery (HUA), the effects of a series of vasoconstrictors were compared in ring preparations with and without endothelium at low (2.5% O2, PO2 < 55 mmHg (1 mmHg = 133.3 Pa)) and high PO2 (95% O2, PO2 > 600 mmHg). The results demonstrate the following. (i) 5-Hydroxytryptamine (5-HT) and endothelin-1 (ET-1) contracted the HUA at either low or high PO2. At low PO2, removal of the endothelium significantly reduced receptor-mediated responses. (ii) The nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not modulate 5-HT-initiated contractions at either level of PO2. (iii) alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT) and 5-carboxamidotryptamine (5-CT), relatively selective 5-HT1C/5-HT2 and 5-HT1-like receptor agonists, respectively, elicited contractions in the HUA, and the responses were reduced at low PO2 but unaffected by removal of the endothelium. (iv) Responses of the HUA to high potassium (hK+) were unaffected by either changes in PO2 or removal of the endothelium. (v) The 5-HT2 receptor antagonist ketanserin at low concentration (10 nM) inhibited contractile responses to 5-HT in an apparently competitive manner. However, with 100 nM ketanserin and at low PO2, inhibition became noncompetitive. Removal of the endothelium did not influence the action of ketanserin. (vi) Regardless of PO2, the Ca2+ channel antagonist nifedipine (1 microM) significantly inhibited 5-HT- and ET-1-mediated contractions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The endothelium contributes to the contractile responses of the human umbilical artery to 5-hydroxytryptamine and endothelin-1 under low but not high PO2 conditions. 788 82

5-hydroxytryptamine (5-HT) has been reported to show some effects in respiratory tissues by activation of different subtype receptors. It has been demonstrated that 5-HT2 receptor activation causes in vivo and in vitro airways contraction and enhances effects of cholinergic nerve-mediated responses, whereas 5-HT1 receptor activation seems to be related to a relaxant effect. Moreover, in isolated guinea pig ascendens colon preparations 5-HT1 activation causes relaxation by involvement of nitric oxide (NO). The aim of this study was to investigate the effects of 5-HT1 receptor activation in guinea pig trachea as well as NO probable role in this activation. In tissues pretreated with both ketanserin (10 microM), an antagonist of 5-HT2 receptors, and ondansetron (10 microM), an antagonist of 5-HT3 receptors, 5-HT (from 10 nM to 10 mM) relaxed guinea pig trachea precontracted with acetylcholine (ACh, 100 microM). Carboxamidotryptamine (5-CT, from 10 nM to 10 mM), an agonist of 5-HT1 receptors, as well relaxed guinea pig trachea precontracted with ACh (100 microM). A pretreatment with NAN-190 (from 10 nM to 100 microM), a 5-HT1A selective antagonist, reduced the 5-HT and 5-CT relaxant effects but only at very high concentrations. Finally, a pretreatment with L-nitro-arginine-methyl-ester (L-NAME, 1 mM), an inhibitor of NO-synthase, and L-arginine (L-ARG, 1 mM), a precursor of NO synthesis, did not modify 5-HT and 5-CT responses in guinea pig trachea. In conclusion, this study suggests a 5-HT relaxant activity in guinea pig trachea via a 5-HT1 receptor activation without any NO pathway involvement. However, further investigations are needed to clarify which 5-HT1 receptor subtype is involved in 5-HT relaxant effect.
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PMID:Effects of in vitro 5-HT1 receptor activation in guinea pig trachea. 869 22

1. The mechanism of action of sumatriptan on coronary flow was examined before and after two different forms of endothelial ablation in guinea-pig isolated hearts. The mechanism was assessed in terms of the influence of the integrity of the coronary endothelium, the role of release of nitric oxide (NO) from the endothelium, and the receptor subtypes mediating the effects. 2. Continuous perfusion with sumatriptan reduced coronary flow, but the concentration-response curve was v-shaped. Sumatriptan (0.001-0.1 microM) caused a concentration-dependent decrease in coronary flow with the maximum effect achieved at 0.23 +/- 0.04 microM. The pEC50 was 8.49 +/- 0.07. At higher concentrations (0.1-10 microM) there was a concentration-dependent diminution of the vasoconstrictor effect. Endothelial ablation by saponin removed the diminution in the vasoconstrictor effect. In contrast pretreatment with NG-nitro L-arginine methyl ester (L-NAME) (100 microM. 45 min perfusion) did not affect it. This was despite both saponin and L-NAME being effective in reducing basal release of NO into the coronary effluent (measured by chemiluminescence) to the same extent (71 +/- 3 and 73 +/- 2%, respectively). 3. GR127935, a selective 5-hydroxytryptamine1D (5-HT1D) receptor antagonist (3 and 10 nM), which by itself had no effect on coronary flow or NO release, antagonized the vasoconstrictor response to sumatriptan and unmasked a sumatriptan-induced concentration-dependent increase in coronary flow and NO release. These increases in coronary flow and NO release were abolished by pretreatment with either saponin or L-NAME. 4. Mesulergine, a 5-HT2 receptor antagonist which had no effect by itself on basal coronary flow or NO release, inhibited the vasodilator response to sumatriptan that occurred in the presence of GR127935, and actually enhanced the vasoconstrictor response, increasing the max mum fall in coronary flow from -3.9 +/- 0.4 to -5.2 +/- 0.4 ml min-1 g-1 (P < 0.05). The diminution of vasoconstrictor effect of sumatriptan was abolished by mesulergine and by pretreatment with saponin, but not by L-NAME. 5. In conclusion, guinea-pig coronary arteries constrict to low concentrations of sumatriptan, causing a reduction in coronary flow. This effect appears to be caused by 5-HT1D agonism with the receptors located on the coronary vascular smooth muscle. With higher concentrations of sumatriptan this is partially offset by a weaker vasodilator effect, which is caused by low affinity 5-HT2 agonism. Although this effect is endothelium-dependent. It is not caused by the release of NO. Interestingly, when the vasoconstrictor effect of sumatriptan was inhibited by the 5-HT1D antagonist GR127935, a high affinity vasodilator effect of sumatriptan was unmasked. This is 5-HT2 receptor mediated and is caused by release of NO from the coronary endothelium. 6. In man, sumatriptan, and 5-HT may both be capable of causing pathogenic coronary vasoconstriction. The implications of the present data are that the scope for this may depend greatly on (i) the extent of underlying endothelial dysfunction, (ii) the extent of endothelial 5-HT2 receptor-mediated release of vasodilator autacoids (which include NO) and (iii) the extent of smooth muscle 5-HT1D receptor-mediated vasoconstriction.
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PMID:Mechanism of actions of sumatriptan on coronary flow before and after endothelial dysfunction in guinea-pig isolated heart. 913 15

We found previously that the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced 2-deoxy-D-glucose (2-DG)-induced hyperphagia in rats. To clarify the involvement of 5-HT, we investigated the effects of 5-HT receptor antagonists on inhibitory effects of L-NAME on 2-DG-induced hyperphagia. The effects of L-NAME on 2-DG-induced hyperphagia were inhibited by the 5-HT1B receptor antagonist metergoline. However, the 5-HT2 receptor antagonist ritanserin had no such effect. These results suggest that the anorectic effects of L-NAME may be related to serotonergic mechanisms.
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PMID:The involvement of 5-HT1B receptors in the inhibitory effects of nitric oxide synthase inhibitor on 2-deoxy-D-glucose-induced hyperphagia in rats. 929 9

1. Vasoconstrictor responses to 5-HT, 5-carboxamidotryptamine (5-CT, 5-HT1 receptor agonist), alpha-methyl-5-HT (5-HT2 receptor agonist) and sumatriptan (5-HT1D/1B receptor agonist) were studied in fetal, 0-24 h, 4 day, 7 day and adult rabbit pulmonary resistance arteries (PRAs), alone and in the presence of the NO synthase inhibitor Nomega-nitro-L-arginine methylester (L-NAME). The effect of the selective 5-HT receptor antagonists ketanserin (5-HT2A receptor) and GR55562 (5-HT1B/1D receptor) on vasoconstrictor responses to 5-HT were studied in the presence of L-NAME. Vasodilator responses to 5-CT were also studied in pre-contracted PRAs. 3. 5-HT and alpha-methyl-5-HT were equipotent in causing contraction in the PRAs at each age (e.g. pEC50s for 5-HT and alpha-methyl-5-HT were 6.74+/-0.13 and 6.63+/-0.22 respectively in adult vessels). In the perinatal PRAs, sumatriptan and 5-CT produced negligible contractions, but in adult PRAs, 5-CT and sumatriptan were potent agonists with pEC50s of 6.05+/-0.3 and 5.70+/-0.20 respectively. 4. L-NAME markedly increased the maximum response to 5-HT in the 0-24 h, 4 day and 7 day vessels and increased 5-HT potency in the 4-, 7-day-old and adult rabbit vessels. 5. In perinatal vessels, responses to 5-HT, with L-NAME present, were antagonized by ketanserin (30 nM and 0.1 microM) but not GR55562 (1 microM). A small ketanserin-resistant, GR55562-sensitive component was observed at 0-24 h. In adult vessels, both ketanserin and GR55562 inhibited 5-HT-induced responses. 7. Vasodilator responses to 5-CT were observed in pre-contracted PRAs from 4- and 7-day-old rabbits but not in the fetus, 0-24 h old or adult rabbit vessels. At 4 days the vasodilator response was inhibited both by L-NAME and GR55562. At 7 days the response was only partly blocked by L-NAME and resistant to GR55562. The L-NAME resistant component was antagonized by the 5-HT7 receptor antagonist spiperone (1 microM). 8. The results suggest that 5-HT2A-receptors mediate vasoconstriction in perinatal vessels whilst the 5-HT1D or 5-HT1B receptor contributes in adult rabbit vessels. The 5-HT1D or 5-HT1B receptor mediates NO-dependent vasodilation in vessels from rabbits at 4 days of age whilst 5-HT7 receptors mediate NO-independent vasodilation by 7 days.
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PMID:5-hydroxytryptamine receptors mediating vasoconstriction and vasodilation in perinatal and adult rabbit small pulmonary arteries. 977 46

We have previously reported that (+/-)-1-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 receptor agonist, induced renal vasodilation in anesthetized dogs. The present study was designed to investigate whether DOI-induced renal vasodilation might be mediated by increased nitric oxide (NO) release/production in renal tissue. The experiments were performed in anesthetized dogs. A 23-gauge needle was inserted into the left renal artery for infusion of drug solutions. Renal blood flow was measured with an electromagnetic flowmeter. The microdialysis probes were implanted into the renal cortex to collect the dialysate for measurement of guanosine 3',5'-cyclic monophosphate (cGMP) and nitrite/nitrate (NO2/NO3) concentration. Intrarenal infusion of DOI at a rate of 5 microg/kg/min resulted in a significant increase, by 30 +/- 4%, in renal blood flow, indicating renal vasodilation. The renal interstitial concentrations of NO2/NO3 and cGMP also increased by 70 +/- 6% and 60 +/- 6%, respectively. These changes induced by DOI were completely abolished by the intrarenal pretreatment with N(w)-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor, 100 microg/kg/min) or sarpogrelate (100 microg/kg/min, a highly selective 5-HT2 receptor antagonist). DOI infusion increased urine volume and urinary excretion of Na+, which were also blocked by L-NAME or sarpogrelate. These results suggest that DOI caused renal vasodilation due to increased NO release/production by stimulation of 5-HT2 receptors in the kidney. The natriuretic effect of DOI might also be related to increased intrarenal NO production.
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PMID:DOI, a 5-HT2 receptor agonist, induces renal vasodilation via nitric oxide in anesthetized dogs. 1186 43

The compound m-chlorophenylpiperazine (mCPP), which is known to trigger migraine-like head pain in some subjects, was evaluated for its ability to induce dural plasma protein extravasation (PPE) in guinea pigs. Intravenous mCPP dose-dependently increased PPE. This effect was inhibited by non-selective 5-HT2 receptor antagonists (methysergide, LY53857, LY215840), by a peripherally restricted 5-HT2 receptor antagonist (xylamidine) and by a 5-HT2B selective receptor antagonist (LY202146). These data suggests that peripheral 5-HT2B receptors mediate mCPP-induced PPE. The nitric oxide synthase inhibitor L-NAME and 5-HT1 agonist sumatriptan also blocked mCPP-induced PPE, suggesting a role for nitric oxide (NO) and the trigeminal system, respectively. NO release has been linked to activation of the 5-HT2B receptor on the vascular endothelium. However, LY202146 did not block PPE induced by electrical stimulation of the trigeminal ganglion. These data are consistent with activation of peripheral 5-HT2B receptors initiating PPE and the theory that selective 5-HT2B antagonists might be effective prophylactic therapies for migraine.
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PMID:Neurogenic dural protein extravasation induced by meta-chlorophenylpiperazine (mCPP) involves nitric oxide and 5-HT2B receptor activation. 1260 68