Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane potential changes induced by 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA) and 1,1-dimethyl-4-phenyl piperazinium (DMPP) were recorded from nodose ganglia (NG) by the sucrose-gap method. An amount of 0.002-0.5 mumol of the depolarizing agent was injected into the superfusion stream to the ganglion. Responses to 5-HT were also evoked from superior cervical (SCG) and dorsal root ganglia (DRG). 5-Hydroxytryptamine elicited depolarizations of graded amplitude. Maximal responses were 4.5 +/- 0.4 mV in nodose ganglia compared to 2.2 +/- 0.2 mV in superior cervical and 0.6 +/- 0.1 mV in dorsal root ganglia (means +/- SEM). In nodose ganglia, GABA induced smaller maximal depolarizations than did 5-HT, similar to those evoked by DMPP; dopamine was a weak depolarizing agent while substance P was apparently inactive. The dose-response curve for 5-HT in nodose ganglia was parallel to that for 5-HT in superior cervical ganglia and significantly to the left (ED50 values 0.029 and 0.098 mumol). Curves for 5-HT and GABA in nodose ganglia were superimposable. The high sensitivity of nodose ganglia cells to 5-HT is briefly discussed. Analogues of 5-HT lacking a hydroxyl group at position 5 on the nucleus were relatively inactive as depolarizing agents. Picrotoxin (10(-6)-10(-5) M) reduced or suppressed responses in nodose ganglia to GABA, whereas responses to 5-HT and DMPP were not much affected or, in the case of 5-HT, sometimes somewhat reduced. Quipazine (10(-6) M) was a selective antagonist of 5-HT responses in nodose ganglia; those to GABA and DMPP were not significantly altered. Neither trazodone nor LSD displayed antagonist properties at 5-HT receptors in nodose ganglia.
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PMID:Depolarizing responses recorded from nodose ganglion cells of the rabbit evoked by 5-hydroxytryptamine and other substances. 706 7

The effects of serotonin on PRL and GH secretion were studied in normal and pituitary stalk-sectioned female rhesus monkeys. Serotonin was administered iv at doses of 50, 500, 5000 microgram. Pretreatment concentrations of serum PRL were elevated in stalk-sectioned monkeys compared to normal monkeys [34 +/- 5 vs. 3 +/- 1 ng/ml (mean +/- SEM)], while serum GH concentrations were lower in the stalk-sectioned animals (< 0.5 vs. 1.3 +/- 0.2 ng/ml). In both normal and stalk-sectioned monkeys, the 5-microgram dose of serotonin failed to alter PRL concentrations. However, with the 500-microgram dose, PRL rose from 3 +/- 1 to 22 +/- 6 ng/ml in normal monkeys and from 27 +/- 6 to 57 +/- 10 ng/ml in stalk-sectioned monkeys. Likewise, with the 5000-microgram dose, PRL rose from 4 +/- 2 to 82 +/- 27 and from 30 +/- 6 to 75 +/- 26 ng/ml in the two respective groups. No dose of serotonin stimulated GH secretion in stalk-sectioned monkeys, although GH did increase from approximately 2 to 4-11 ng/ml in normal monkeys. Since the pituitary is devoid of direct hypothalamic influences in the pituitary stalk-sectioned animals, these results suggest that serotonin can modulate PRL secretion either directly at the pituitary level or via some yet to be determined peripheral mechanism. In contrast, this neurotransmitter appears to incorporate hypothalamic factors in its modulation of GH secretion.
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PMID:The effects of serotonin on prolactin and growth hormone concentrations in normal and pituitary stalk-sectioned monkeys. 742 89

The ontogenic destruction of dopamine (DA) neurons in rat brain is associated with supersensitization of DA D1 receptors. This effect is attenuated when rats are cotreated in ontogeny with the serotonin (5-HT) neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). In an attempt to determine whether 5-HT fibers might have a similar modulatory role on the sensitivity of the DA D2 receptor complex, we pretreated rats with desipramine HCl (20 mg/kg, IP, base), 1 h before the DA neurotoxin, 6-hydroxydopamine (6-OHDA; 134 micrograms ICV, base) and/or 5,7-DHT (75 micrograms ICV) and/or vehicle. At about 3 months after birth dose-effect curves for quinpirole-induced oral activity were constructed for each group of rats. We found that quinpirole, an agonist for the DA D2 receptor complex, produced a dose-related increase in oral activity in all groups of rats. After a 200 micrograms/kg dose of quinpirole HCl, however, neonatal 5,7-DHT-lesioned rats had a peak oral response of 54.4 +/- 5.1 (mean and SEM) vs. 22.6 +/- 4.8 for control rats (p < 0.01). In neonatal 6-OHDA-lesioned rats this dose of quinpirole increased oral activity to 36.8 +/- 5.8 oral movements (p < 0.05 vs. control). In rats lesioned with both 5,7-DHT and 6-OHDA, the oral response was not different from control. The enhanced oral response to quinpirole in 5,7-DHT-lesioned rats was attenuated by spiperone, an antagonist for the DA D2 receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced quinpirole response in rats lesioned neonatally with 5,7-dihydroxytryptamine. 761 14

Acute systemic injection of selective serotonin reuptake inhibitors (SSRIs) decreases 5-HT neuronal firing in the dorsal raphe nucleus (DRN). Recent data, however, question whether these drugs also inhibit the firing of 5-HT neurones in the median raphe nucleus (MRN). Using in vivo extracellular electrophysiological recording techniques in the chloral hydrate anaesthetised rat, we have tested the effect of acute administration of the SSRI, paroxetine, on 5-HT neuronal activity in the MRN and DRN. Presumed 5-HT neurones in the MRN displayed the same electrophysiological characteristics as those in the DRN, the only detectable difference being that MRN neurones showed a significantly (p < 0.001) slower mean (+/- SEM(n)) spontaneous firing rate (MRN, 5.6 +/- 0.9 (14) spikes/10 s; DRN, 13.5 +/- 1.6 (24) spikes/10 s). Paroxetine caused a dose-related (0.1-0.8 mg/kg i.v.) inhibition of all MRN neurons tested (n = 8), producing a complete cessation of cell-firing at the highest doses. DRN neurones (n = 9) responded in a similar fashion. Furthermore, paroxetine inhibited MRN and DRN neurones with almost identical potency (MRN ED50 259 +/- 57 micrograms/kg i.v.: DRN ED50 243 +/- 49 micrograms/kg i.v.). In the majority of cells tested, the effect of paroxetine was reversed by the 5-HT1A receptor antagonists spiperone or (+)WAY100135, implicating the involvement of the 5-HT1A autoreceptor. The selective 5-HT1A receptor agonist 8-OH-DPAT also inhibited the firing of MRN (n = 5) and DRN (n = 12) neurones and with equal potency (MRN ED50, 1.32 +/- 0.40 microgram/kg i.v.: DRN ED50, 1.19 +/- 0.23 microgram/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of median and dorsal raphe neurones following administration of the selective serotonin reuptake inhibitor paroxetine. 767 21

Single photon emission computed tomography (SPECT) studies of regional kinetic uptake and pharmacological specificity of [123I]methyl 3 beta-(4-iodophenyl) tropane-2 beta-carboxylate ([123I]beta-CIT) were performed in nonhuman primates (n = 41). In control experiments, activity was concentrated in striatum and in hypothalamic/midbrain regions. Striatal uptake increased for 140-180 min and displayed stable levels thereafter. Striatal to cerebellar activity ratios were 7.3 +/- 0.9 (mean +/- SEM) at 300 min. About 75% of striatal uptake was displaceable by injection of nonradioactive beta-CIT. Hypothalamic/midbrain activity reached maximal levels at approximately 45 min. A slow washout phase followed this peak activity. Activities in frontal, occipital, and cerebellar regions were characterized by an early peak (20-30 min), followed by rapid washout. Displacement studies demonstrated that striatal uptake was associated with dopamine (DA) transporters, as it was displaced by GBR 12909, a selective DA uptake inhibitor, but not by citalopram, a selective serotonin (5-HT) uptake inhibitor. The inverse was true in the hypothalamic/midbrain area, suggesting that the uptake in this area was associated primarily with 5-HT transporters. Maprotiline, a selective norepinephrine uptake inhibitor, did not affect [123I]beta-CIT uptake. In vivo site occupancy ED50 values of cocaine, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (CFT), and beta-CIT were measured in the striatum with a stepwise displacement paradigm. In vivo ED50 values correlated strongly with in vitro IC50 values for binding to DA transporters. Infusion of high dose of L-DOPA (250 mumol/kg) failed to displace striatal [123I]beta-CIT binding, suggesting that the binding would not be affected by L-DOPA administration in Parkinsonian patients. However, studies performed with injection of d-amphetamine indirectly suggested that high synaptic levels of DA may compete with [123I]beta-CIT binding. These studies suggest that [123I]beta-CIT will be a useful SPECT tracer of DA and 5-HT transporters in living human brain.
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PMID:SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT: pharmacological characterization of brain uptake in nonhuman primates. 768 43

A clonal cell line derived from rat renal mesangial cells was shown to express endogenous 5-hydroxytryptamine (serotonin, 5-HT) receptors that mediate inhibition of cyclic AMP accumulation. These receptors were characterized as being of the 5-HT1B receptor subtype. 5-HT1 receptor agonists inhibited forskolin-stimulated cyclic AMP accumulation in rat renal mesangial cells (60-70% maximal inhibition) with the following rank order of potency (mean pEC50 values +/- SEM, n > or = 3): ergotamine (9.58 +/- 0.51) > RU 24969 (8.67 +/- 0.23) > or = 5-CT (8.42 +/- 0.06) > or = CP 93129 (8.15 +/- 0.27) > 5-HT (7.75 +/- 0.11) > sumatriptan (6.29 +/- 0.30) > 8-OH-DPAT (4.32 +/- 0.15). 5-HT2 and 5-HT4 receptor agonists were without effect. 5-HT-induced inhibition of cyclic AMP accumulation was abolished by a pre-treatment of the cells with pertussis toxin. (-)Propranolol was a partial agonist (27% maximal inhibition, pEC50 7.19 +/- 0.24, n = 3); when used as an antagonist at 1 microM, it shifted the concentration-response curve of 5-HT to the right (pKB 7.22 +/- 0.35, n = 3). Methiothepin was a competitive antagonist of 5-HT (pA2 8.04 +/- 0.10, Schild slope 0.87 +/- 0.21, n = 3). Rauwolscine (10 microM) had no antagonist activity. There was a significant correlation (r = 0.98, P = 0.0001) between the cyclic AMP data obtained in rat mesangial cells and 5-HT1B binding data reported in rat brain cortex. The same pattern of responses was observed in early passages of primary cultures of rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-Hydroxytryptamine 5-HT1B receptors inhibiting cyclic AMP accumulation in rat renal mesangial cells. 771 39

Serotonin (5-HT) efflux in slices of rat dorsal raphe nucleus (DRN) was evoked by pseudo one pulse electrical stimulation (20 pulses at 100 Hz, 190 ms train duration) and measured, along with 5-HT uptake, by fast cyclic voltammetry (FCV). The selective serotonin re-uptake inhibitor (SSRI) paroxetine (10(-7) M) increased 5-HT efflux to 147 +/- 6% of pre-drug values at maximum (mean +/- SEM, n = 5) and the half-life of uptake to 443 +/- 38%. The non-selective 5-HT1 antagonist methiothepin (2 x 10(-7) M) increased 5-HT efflux to 147 +/- 9% at maximum but had no effect on uptake half-life. In contrast, (+)-WAY 100135 (10(-6) M) and GR 127935 (5 x 10(-8) M), selective antagonists at 5-HT1A and 5-HT1B/D receptors, respectively, affected neither 5-HT efflux nor uptake. When given in combination with paroxetine, the antagonists significantly increased the effect of paroxetine on efflux: methiothepin to 228 +/- 24% (P < 0.001), (+)-WAY 100135 to 212 +/- 31% (P < 0.05) and GR 127935 to 203 +/- 23% (P < 0.01). These data suggest that, under these experimental conditions, DRN 5-HT autoreceptors are tonically activated in the presence of the uptake blocker and that the antagonists act by blocking this counteracting autoinhibitory tone. The data also strongly indicate that 5-HT efflux in the rat DRN is under the control not only of 5-HT1A but also of 5-HT1B/D receptors.
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PMID:The effect of paroxetine on 5-HT efflux in the rat dorsal raphe nucleus is potentiated by both 5-HT1A and 5-HT1B/D receptor antagonists. 778 75

The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonist, ICS 205-930 (tropisetron), on basal and 5-HT induced jejunal secretion of water and electrolytes were examined using a double blind, randomised crossover design. In seven healthy volunteers steady state perfusions of the proximal jejunum were performed twice with the Loc-I-Gut tube after 5+5 mg ICS 205-930 or placebo capsules were given. After equilibration for 60 minutes and completion of a 120 minute basal period 5-HT (10 micrograms/kg x min intravenously) was infused for 120 minutes. Net water absorption (mean (SEM)) in the basal period was 0.55 (0.84) ml/cm x h and 0.74 (0.72) ml/cm x h after placebo and ICS 205-930, respectively (p > 0.05). Infusion of 5-HT caused significant net secretion of water after placebo (2.05 (0.58) ml/cm x h; p < 0.02) as well as ICS 205-930 (2.60 (0.89) ml/cm x h; p < 0.05). As ICS 205-930 excerted no effects on either basal or 5-HT induced water and electrolyte transport in the intact human jejunum the compound is probably not efficacious as an anti-secretory drug in patients with 5-HT induced diarrhoea.
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PMID:Failure of tropisetron to inhibit jejunal water and electrolyte secretion induced by 5-hydroxytryptamine in healthy volunteers. 820 May 56

Earlier generations of excimer lasers, designed for industrial or non-cardiovascular medical applications, have been previously shown consistently to induce vasorelaxation of vascular smooth muscle in vitro. Such lasers were typically characterized by pulse durations of < or = 15 nanoseconds (ns). Excimer lasers currently employed for cardiovascular applications were designed with longer pulse durations (up to 220 ns) to facilitate fibreoptic transmission. Because arterial spasm has been observed in patients undergoing percutaneous revascularization with such lasers, we investigated the effect of so-called 'stretched pulse' excimer laser irradiation on vasomotor reactivity. A total of 69 rings of aorta harvested from New Zealand white rabbits were mounted isometrically in Krebs buffer solution and exposed to 308 nm from an excimer laser with a pulse duration of 120 ns. Fifty rings were exposed without pharmacological pre-treatment. The remaining 19 rings were exposed after pharmacological pre-treatment: 11 were precontracted with norepinephrine (NE, 10(-9)-10(-5) M), while eight were irradiated in Ca(2+)-free buffer after pre-relaxation with nitroglycerin (NTG, 7 x 10(-5) M). Without pharmacological pre-treatment, the vasomotor response to the excimer laser was variable: vasoconstriction was observed in 27 rings (16.1 +/- 0.8% (mean +/- SEM) of response to 5-HT), vasorelaxation in 21 rings (43.2 +/- 17.0% of response to 5-HT), and a heterogeneous response (vasoconstriction 4.9 +/- 1.0%, vasorelaxation 12.9 +/- 0.3%) in two rings. The vector of vasomotor response in non-precontracted rings was not predicted by fluence, frequency or temperature rise. A consistent vasomotor response was recorded only when pharmacological pre-treatment was employed. Among 11 rings pre-contracted with NE, the excimer laser produced vasorelaxation in 34/34 (100%) exposures; in contrast, among eight rings pre-relaxed with NTG in Ca(2+)-free buffer, the excimer laser produced vasoconstriction in 40/40 (100%) exposures. For all rings, including pre-contracted, pre-relaxed and those which were not pharmacologically pre-treated, the vector of vasomotor response was endothelium-independent. The magnitude of all vasomotor responses, including vasoconstriction in non-precontracted rings, could be diminished by limiting the duration of exposure. Thus, in contrast to the earlier generation, short-pulse excimer lasers, long pulse-duration excimer lasers in current clinical trials produce an unpredictable, heterogeneous vasomotor response. This in-vitro finding is consistent with the unpredictable development of vascular spasm in patients undergoing excimer laser angioplasty. Furthermore, these findings support the concept of employing abridged pulse trains to diminish the likelihood of laser-induced vasoconstriction during excimer laser angioplasty.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Excimer laser-induced vasoreactivity. 826 87

1. An arylalkylamine N-acetyltransferase (NAT) of the parasitic nematode, Ascaridia galli was studied using either [14C]serotonin (5-HT) or [14C]octopamine (OA) as substrates and with acetyl-CoA as the donor of the acetate group. 2. The NAT activity towards 5-HT and OA co-eluted from a size-exclusion column and appeared to have an M(r) of around 30,000. The enzyme had apparent Km values of 540 +/- 100 microM (+/- SEM) and 33 +/- 4 microM (+/- SEM) for 5-HT and octopamine, respectively, when assayed in the presence of 1 mM acetyl-CoA. 3. High levels of NAT were found in the gonads of male and female worms and the muscle/body wall. 4. N-acetylation was strongly inhibited by Cu2+ but not by other divalent metal ions and the effect of a number of compounds including biogenic amines, formamidines, hydrazines, and beta-carbolines on the arylalkylamine N-acetyltransferase activity was studied.
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PMID:Properties of an arylalkylamine N-acetyltransferase from the nematode, Ascaridia galli. 829 55


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