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

1. The emetic potencies of morphine and its metabolite morphine 6-glucuronide have been determined in the ferret by constructing dose-response curves for mean total retches and vomits for subcutaneous doses of 0.05 mg kg-1 to 5 mg kg-1. Morphine 6-glucuronide induced retching and vomiting at lower doses than morphine and at a maximal dose induced more retching and vomiting than morphine. 2. The emesis induced by both morphine and morphine 6-glucuronide was abolished by the preadministration of naloxone (0.5 mg kg-1 s.c.). 3. The 5-HT3 receptor antagonists granisetron and ondansetron (1 mg kg-1, s.c.) failed to abolish or reduce emesis induced by either compound. 4. At a high-dose (5 mg kg-1), morphine but not morphine 6-glucuronide failed to induce emesis and abolished the emesis induced by the cytotoxic drug, cyclophosphamide (200 mg kg-1, i.p.). 5. Preliminary pharmacokinetic studies of intravenous and subcutaneous morphine and morphine 6-glucuronide revealed that morphine 6-glucuronide accounts for less than 1% of the metabolic product of morphine in the ferret. Peak plasma levels of the two compounds after their subcutaneous administration were obtained within 10 min. The metabolic profile of morphine was not dose-dependent. There was no relationship between plasma level and emetic response for either compound.
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PMID:Morphine 6-glucuronide: a metabolite of morphine with greater emetic potency than morphine in the ferret. 132 67

The effect of morphine on the ion current mediated by 5-hydroxytryptamine (5-HT3) receptors was investigated in rat nodose ganglion neurons and in Xenopus oocytes expressing the cloned 5-HT3 receptor. Morphine reversibly inhibited the 5-HT-induced current and shifted the 5-HT concentration-response curve to the right in a parallel fashion, without reducing the maximal 5-HT response. IC50 values for morphine were 0.3 microM in nodose neurons and 0.32 microM in oocytes. The apparent Kd of morphine in nodose neurons was 0.903 microM. This effect of morphine was immediate not dependent on membrane potential, and not prevented by the opioid receptor antagonists naltrexone and beta-chlornaltrexamine. It is concluded that opioid receptors were not involved in the present study and that morphine acted at the agonist recognition site located on the 5-HT3 receptor.
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PMID:Nonopioid mechanism of morphine modulation of the activation of 5-hydroxytryptamine type 3 receptors. 753 78

1. Experiments were carried out to characterize the receptors mediating the indirect excitatory response to 5-hydroxytryptamine (5-HT) in the guinea-pig isolated trachea. 2. 5-HT caused concentration-dependent contractions of tracheal strips, and the resulting concentration-response curve was biphasic in nature. The first phase was obtained with agonist concentrations in the range of 0.01-3 nM and achieved a maximum which was 30% of the total 5-HT response, while the second phase was in the range 10 nM-1 microM. 3. Atropine (0.1 microM) and tetrodotoxin (TTX: 0.3 microM) significantly reduced both phases of the 5-HT curve. Morphine (10 microM), which can act to inhibit neuronal acetylcholine release, abolished the first phase and reduced the second phase. This suggests that the first phase is mainly neurogenic (cholinergic) in nature, while the second phase is in part neurogenic and in part due to direct activation of the effector cells. 4. The 5-HT2A receptor antagonist, ketanserin (0.01, 0.1 microM) markedly depressed the first phase and shifted the second phase to the right in a parallel manner, with some depression of the 5-HT response maximum. The less selective (5-HT1/5-HT2A) antagonist, methiothepin (0.1 microM) mimicked the action of ketanserin, albeit with less potency. Concomitant administration of ketanserin and methiothepin (each at 0.1 microM) produced an antagonism similar to that caused by ketanserin (0.1 microM) alone. 5. The 5-HT3 receptor antagonists, ondansetron (0.1 microM) and granisetron (0.01 microM) slightly but significantly inhibited the first phase of the 5-HT curve without altering the second phase. SDZ 205,557(0.3 MicroM), a 5-HT4 receptor antagonist, was ineffective.6. Our results suggest that neural 5-HT2A and, to a lesser extent, 5-HT3 receptor subtypes mediate the first phase of the 5-HT curve in the guinea-pig trachea. The second phase is mediated by 5-HT2Areceptors, which are probably located at both the neural and muscular level. No evidence for the participation of 5-HT1 receptors in the 5-HT response has been obtained.
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PMID:A pharmacological analysis of receptors mediating the excitatory response to 5-hydroxytryptamine in the guinea-pig isolated trachea. 792

The effects of three different 5HT3 receptor antagonists, granisetron, ICS 205-930 and ondansetron (0.01, 0.1 and 1 mg/kg, s.c.) were tested on changes in mesolimbic dopamine function produced by 1 mg/kg of morphine in the rat. Increases of in vivo dopamine release and stimulation of behavioural activity (grooming, locomotion, rearing and sniffing) were monitored. Morphine (0.5 and 1 mg/kg, s.c.) increased dose-dependently the concentration of dopamine in dialysates obtained from the nucleus accumbens. This action of morphine was inhibited by the opiate antagonist naloxone (1 mg/kg, s.c.). Morphine (0.5 and 1 mg/kg) stimulated behavioural activity, which in the early part of the time course corresponded closely with the increase of dopamine in the nucleus accumbens. Pretreatment with 1 mg/kg (s.c.) of granisetron resulted in moderate inhibition (28%) of the morphine-induced stimulation of the extracellular dopamine levels, while doses of 0.01 and 0.1 mg/kg (s.c.) had no effect. The highest dose of granisetron (1 mg/kg, s.c.) also significantly reduced the morphine-induced enhancement of behavioural activity. The fact that granisetron attenuated morphine-induced effects on mesolimbic DA only at the highest dose tested (1 mg/kg, s.c.) was also true for ICS 205-930 and ondansetron. It is concluded that 5HT3 receptor antagonists partially inhibit, with low potency, the morphine-induced stimulation of dopamine release in the nucleus accumbens and the corresponding behavioural activation.
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PMID:5-HT3 receptor antagonists inhibit morphine-induced stimulation of mesolimbic dopamine release and function in the rat. 838 55

This experiment was conducted to determine whether drugs acting on brain serotonin modulate the effects of the mu opioid, morphine, as measured by the squirrel monkey shock titration procedure and, if so, whether serotonergic modulation is mediated via specific 5HT receptor subtypes. Under this procedure, electric shock was delivered to the monkey's tail and scheduled to increase once every 15 s from 0.01 to 2.0 mA in 30 steps. Five responses on a lever during the 15-s shock period terminated the shock for 15 s, after which the shock resumed at the next lower intensity. The intensity below which monkeys maintained shock 50% of the time (median shock level or MSL) and rate of responding (RR) in the presence of shock were determined under control conditions and after administration of morphine alone and in combination with various serotonergic compounds. Morphine increased median shock level and decreased rate of responding in a dose-dependent manner. These effects of morphine was attenuated by the 5HT1A receptor agonists, 8-OH-DPAT [(+)-8-hydroxy-2(di-n-propylamino tetralin HBr] and ipsapirone. The effects of morphine were not altered by the 5HT1A receptor antagonist, NAN-190 [1-(2-methoxyphenyl-4-[4-(2-phthalimido) butyl] piperazine HBr], and 5HT2 receptor antagonist, ketanserin, the 5HT3 receptor antagonist, MDL 72222 [3-tropanyl-3,5-dichlorobenzoate], the alpha 2 adrenergic antagonist, yohimbine, or the alpha2 adrenergic agonist, clonidine. These results suggest that 5HT1A receptors may be involved in the effects of morphine in the shock titration procedure, whereas 5HT2, 5HT3 and alpha 2 adrenergic receptors do not appear to play a role in morphine's effects in this procedure.
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PMID:The role of serotonergic receptors in the effects of mu opioids in squirrel monkeys responding under a titration procedure. 885 15

5-HT3 receptors are ligand-gated ion channels that are involved in the modulation of emesis and pain. In this study, we investigated whether the opioid analgesic, morphine, exerts specific effects on human 5-HT3 receptors. Whole-cell patches from HEK-293 cells stably transfected with the human 5-HT3A receptor cDNA were used to determine the effects of morphine on the 5-HT-induced currents using the patch clamp technique. At negative membrane potentials, 5-HT induced inward currents in a concentration-dependent manner. The 5-HT3 receptor antagonist, ondansetron, (0.3 nM) reversibly inhibited the 5-HT-induced signals. Morphine reversibly suppressed 5-HT-induced peak currents as a function of concentration (IC50 = 1.1 microM, Hill coefficient = 1.2). The block by morphine decreased with increasing 5-HT concentrations, suggesting a competitive effect. In addition, the activation, as well as the inactivation, kinetics of the currents were significantly slowed in the presence of morphine. The morphine antagonist, naloxone, also inhibited 5-HT-induced currents (e.g., at 3 microM by 17%). The effects of morphine and naloxone were not additive. The potency of morphine and the competitivity of the blocking effect points to a specific mechanism at a receptor site rather than an unspecific membrane effect.
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PMID:The effects of morphine on human 5-HT3A receptors. 1693 91