Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A putative 5-HT4 receptor-mediated depolarization of the rat isolated vagus nerve has been studied using a grease-gap extracellular recording technique. Ondansetron (1 microM) was used to block the predominant 5-HT3 receptor mediated depolarization in this preparation and the effects of the 5-HT4 receptor antagonists DAU 6285 (endo-8-methyl-8-azabicyclo [3.2.1] oct-3-yl-2,3-dihydro-6-methoxy-2-oxo-1H-benzimidazole-1- carboxylate HCl); 0.3, 1.0 or 3.0 microM and SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)-ethyl ester HCl); 0.1, 0.3 or 1.0 microM were studied on the residual, ondansetron-resistant, component of the response. The effects of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) and of forskolin on the ondansetron-resistant response were also studied. Both DAU 6285 and SDZ 205-557 acted as competitive antagonists of the ondansetron-resistant response to 5-HT with pA2 values of 6.8 (6.7-7.1, n = 12) and 7.1 (6.9-7.5, n = 12) respectively. The vagus nerve was depolarized by IBMX (100 microM) or forskolin (10 microM), the effects being similar to the maximum response to 5-HT. In the presence of IBMX (100 microM) or forskolin (10 microM) the ondansetron-resistant component of the response to 5-HT was enhanced and the 5-HT3 receptor-mediated component reduced. These results with DAU 6285 and SDZ 205-557 are consistent with a 5-HT4 receptor-mediated mechanism of the ondansetron-resistant depolarizing response to 5-HT.
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PMID:Further characterization of the putative 5-HT4 receptor mediating depolarization of the rat isolated vagus nerve. 747 28

5-Hydroxytryptamine (5-HT) contracts and relaxes isolated stomach preparations. This study attempts to characterise receptors involved in the contractile response using electrically stimulated circular muscle strips from guinea pig stomach. Electrically induced contractions were abolished by atropine and tetrodotoxin. 5-HT enhanced contractions in corpus and fundus strips with pEC50% values (-log10 of the concentrations causing a 50% increase in twitch height) of 9.6 and 9.1, respectively. 5-Carboxamidotryptamine and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), 5-HT1A receptor agonists, and alpha-methyl-5-HT, an agonist at 5-HT2 receptors, reduced contractions. The 5-HT3 receptor agonist, 2-methyl-5-HT, increased contractions. The effect of 2-methyl-5-HT but not of 5-HT was antagonized by the 5-HT3 receptor antagonist, tropisetron (10(-7) M). The 5-HT3 receptor antagonists, tropisetron, MDL 72222 (1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoate), grainsetron and ondansetron, did not modify twitch responses at concentrations below 10(-7) M. Renzapride and metoclopramide, agonists at 5-HT4 receptors, increased contractions and this effect was inhibited by the 5-HT4 receptor antagonist SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester) with a pA2 of 7.4. The effect of 5-HT at a submaximal concentration of 10(-8) M was blocked by SDZ 205-557 (10(-6) M). It is concluded that electrically induced contractions in guinea pig stomach strips are enhanced by activation of 5-HT3- and 5-HT4 receptors and are diminished by 5-HT1 receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulant effects of 5-hydroxytryptamine on guinea pig stomach preparations in vitro. 781 82

1. The interaction of the novel antagonist, SDZ 205,557 (2-methoxy-4-amino-5-chloro benzoic acid 2-(diethylamino) ethyl ester), at 5-HT3 and 5-HT4 receptors has been assessed in vitro and in vivo. 2. In guinea-pig hippocampus and in the presence of 0.4 microM 5-carboxamidotryptamine, 5-HT4-mediated stimulation of adenylyl cyclase was competitively antagonized by SDZ 205,557, with a pA2 value of 7.5, and a Schild slope of 0.81. In rat carbachol-contracted oesophagus, 5-HT4-receptor mediated relaxations were surmountably antagonized by SDZ 205,557 with a similar pA2 value (7.3). This value was agonist-independent with the exception of (R)-zacopride, against which a significantly lower value (6.4) was observed. 3. In functional studies of 5-HT3 receptors, SDZ 205,557 exhibited an affinity of 6.2 in guinea-pig ileum compared with 6.9 at binding sites labelled by [3H]-quipazine in NG108-15 cells. In the anaesthetized, vagotomized micropig, SDZ 205,557 produced only a transient blockade of 5-HT4-mediated tachycardia. This contrasted with tropisetron, which was active for over 60 min after administration. The half-lives for the inhibitory responses of SDZ 205,557 and tropisetron were 23 and 116 min, respectively. 4. In conclusion, SDZ 205,557 has similar affinity for 5-HT3 and 5-HT4 receptors. The apparent selectivity observed in guinea-pig is due to the atypical nature of the 5-HT3 receptor in this species. The short duration of action of this novel antagonist may complicate its use in vivo. SDZ 205,557 should, therefore, be used with appropriate caution in studies defining the 5-HT4 receptor.
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PMID:The action of SDZ 205,557 at 5-hydroxytryptamine (5-HT3 and 5-HT4) receptors. 844 87

It has long been thought that intestinal absorption of most of the drugs proceeds by passive diffusion mechanism, in which lipid solubility of the drug molecule is a determinant factor. However, water-soluble natural compounds such as amino acids and sugars can move across cell membranes by the specialized carrier-mediated transport mechanisms. Although some drugs which are structurally analogous to natural compounds have been suggested to be absorbed by such transporters, no clear evidence for the involvement of carrier-mediated transport mechanisms has been obtained. In the present study, through the approach by means of the molecular cloning and functional expression of drug transporters as well as membrane physiological analysis for the drug transport across the intestinal epithelial cell membranes, participation of the carrier-mediated transport mechanisms for the drug absorption was clarified. They include peptide transporter, monocarboxylic acid transporter, anion antiporter, and P-glycoprotein. Most of them have a function for the uptake of drugs into epithelial cells, leading to the increased absorption of drugs, whereas P-glycoprotein excludes drugs into the lumen, thereby decreasing the apparent absorbability of drugs. A rat intestinal monocarboxylic acid-proton cotransporter, MCT1, and an anion antiporter, AE2, were suggested to contribute to the pH-dependent intestinal absorption of monocarboxylic acids such as benzoic acid, lactic acid, nicotinic acid, and valproic acid. An involvement of such pH-dependent transporters in the intestinal absorption of weak organic acids is important, because they may have an alternative mechanism against passive diffusion according to the pH-partition hypothesis. PepT1 cloned from rat intestinal epithelial cells as a peptide transporter was clarified to localize at the intestinal epithelia brush-border membrane and to function for the absorption of beta-lactam antibiotics by the proton-gradient energized mechanism. In contrast, P-glycoprotein functions for the secretion of drugs into the intestinal lumen, thereby decreasing intestinal absorption of an immunosuppressive, cyclosporin A and a 5-HT3 receptor antagonist, azasetron. These lines of studies on the clarification of carrier-mediated drug absorption mechanisms will provide new knowledge for the strategies to the enhancement of intestinal absorption of drugs.
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PMID:[Molecular characterization of intestinal absorption of drugs by carrier-mediated transport mechanisms]. 926 Dec 13

The effects of neferine, an alkaloid of Nelumbo nucifera Gaertner embryos, on immobility in the forced swimming test, which is used to evaluate antidepressants, were investigated in mice. The administration of neferine from 25 to 100 mg/kg i.p. elicited anti-immobility effects in mice. The molecular dose effects of neferine in the forced swimming test were almost equal to those of the typical antidepressants maprotiline and imipramine. The involvement of the 5-HT receptor subtypes was also studied using 5-HT receptor antagonists. Anti-immobility effects of neferine are antagonized by the serotonin1A (5-HT1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). However, the 5-HT1B receptor antagonist, 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl] benzamide dihydrochloride (GR 55562), the 5-HT2 receptor antagonist, 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY 53857), the 5-HT3 receptor antagonist, ondansetron and the 5-HT4 receptor antagonist, 4-amino-5-chloro-2-methoxy-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205,557) did not affect the anti-immobility effects of neferine. The anti-immobility effect of the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetaralin (8-OH-DPAT) was also antagonized by WAY 100635. Furthermore, co-administration of subactive doses of neferine (10 mg/kg) and 8-OH-DPAT (0.1 mg/kg) produced synergistic antidepressant-like effects. These results suggest that neferine shows antidepressant-like effects in mice similar to typical antidepressants and that these effects are mediated by the 5-HT1A receptor. Therefore, the central effects of neferine are likely to be linked to serotonergic neurotransmission.
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PMID:Antidepressant-like effects of neferine in the forced swimming test involve the serotonin1A (5-HT1A) receptor in mice. 2017 13