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

Superfusion of hemisected lumbar spinal cord of the neonatal rat with solutions containing 10(-6) to 10(-3) M 5-hydroxytryptamine (5-HT) elicited depolarizations of graded amplitude which were recorded from motorneurons through a ventral root. Maximum responses (amplitude 1.0 +/- 0.1 mV, mean +/- SEM, n = 30) were evoked by 10(-4) M 5-HT. Repeated concentration-response curves could be determined from the same preparation. There was no involvement of 5-HT2 receptors in the depolarizing response to 5-HT, since neither ritanserin nor ICI 169, 369 showed any antagonist action. Amongst agents with activity at 5-HT1A sites, the selective 5-HT1A receptor agonist, 8-hydyroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), neither mimicked the action of 5-HT nor antagonised it, while spiperone (10(-8)-10(-7 M) antagonised responses to 5-HT in a concentration-related manner. Responses to 10(-4) M noradrenaline, used as a control depolarizing agent, were unaffected by spiperone. The onset of blockade by spiperone was slow, 1 hr being required for equilibration of the tissue with antagonist. The blockade was surmountable by larger concentrations of 5-HT. Concentration-response curves to 5-HT were shifted to the right in an approximately parallel manner by spiperone. The dose ratios measured from these curves at the EC50 level, yielded an apparent pA2 of 8.24 +/- 0.14 (mean +/- SEM, n = 15), although the Schild plot of the data had a slope less than unity. The lack of activity of the selective 5-HT1B receptor agonist, RU 24969, and the 5-HT1B receptor antagonists, (+/-) cyanopindolol and quipazine, indicated that 5-HT1B receptors were not involved in the 5-HT response of motorneurones to 5-HT. Mesulergine, metergoline and cyproheptadine also antagonised responses of motorneurones to 5-HT, producing a surmountable blockade. Mesulergine (10(-8), 3 x 10(-8) and 10(-7) M caused a progressive rightward shift of the concentration-response curves, but 10(-7) M depressed the maximum response to 5-HT. Responses to noradrenaline were not affected by these concentrations of mesulergine. The apparent pA2 for blockade of 5-HT responses by mesulergine, calculated from experiments in which there was a parallel displacement of the concentration-response curves, was 8.75 +/- 0.11 (mean +/- SEM, n = 10).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:5-Hydroxytryptamine depolarizes neonatal rat motorneurones through a receptor unrelated to an identified binding site. 275 65

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)
 ...
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.
 ...
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

5-Hydroxytryptamine 5-HT1B/5-HT1D receptors are members of the same receptor subfamily, but display a different pharmacology (Hartig et al. (1992) Trends Pharmacol Sci 13: 152-159). Whereas several cell lines have been reported to contain 5-HT1B receptors, none has been described, however, that endogenously expresses well-characterized 5-HT1D receptors. The present study deals with the identification of 5-HT1D receptors inhibiting cyclic AMP accumulation in Madin-Darby canine kidney (MDCK) cells. 5-HT (1 nM-10 microM) induced a concentration-dependent inhibition of the cyclic AMP accumulation stimulated by prostaglandin E1 (1 microM) in MDCK cells. The maximal effect of 5-HT averaged 50% inhibition and was abolished after a pre-treatment of the cells with pertussis toxin. Other agonists mimicked the effects of 5-HT, with the following rank order of potency (pEC50 +/- SEM, n > or = 3): 5-carboxamidotryptamine (8.36 +/- 0.48) > PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine. 7.89 +/- 0.23) > 5-HT (7.35 +/- 0.05) > sumatriptan (6.65 +/- 0.27). PAPP behaved as a partial agonist. 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) was less potent, its maximal effect being not reached at 0.1 mM. Methiothepin. GR127935, (-)propranolol, rauwolscine and ketanserin were all devoid of intrinsic activity (up to 10 microM or 0.1 mM). Methiothepin (10 nM. 0.1 microM and 1 microM) antagonized 5-HT effect (pA2 8.57 +/- 0.44. Schild slope 1.17 +/- 0.21, n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:5-Hydroxytryptamine 5-HT1D receptors mediating inhibition of cyclic AMP accumulation in Madin-Darby canine kidney (MDCK) cells. 858 40

Fast cyclic voltammetry (FCV) was used to measure electrically stimulated monoamine efflux in the rat ventral lateral geniculate nucleus (vLGN). The electrochemical characteristics of the released species resembled 5-HT but not dopamine or noradrenaline. Amine efflux was abolished by the sodium channel blocker tetrodotoxin (0.1 microM), Ro 4-1284 (1.0 microM), the fast-acting reserpine analogue, and removal of Ca2+ from the superfusate. Amine efflux was unaffected by the monoamine oxidase inhibitor clorgyline (0.1 microM). Of paroxetine (0.1 microM), desipramine (50 nM) and vanoxerine (0.5 microM), selective blockers of 5-HT, noradrenaline and dopamine uptake respectively, only paroxetine increased monoamine efflux (to 194 +/- 25%, mean +/- SEM) and prolonged the removal half-life (to 638 +/- 105%). The non-specific 5-HT1 antagonist methiothepin (0.2 microM) increased 5-HT efflux on long (20 pulses at 20 Hz) but not short trains (20 pulses at 100 Hz). When tested on pseudo-one-pulse stimulations (5 pulses, 100 Hz), the selective 5-HT1A agonist 8-OHDPAT (1.0 microM) had no effect. CP 93129 (0.3 microM), the selective 5-HT1B agonist, decreased 5-HT efflux to 37 +/- 4% of control and was antagonised by the 5-HT1B blocker isamoltane (0.5 microM) and by the 5-HT1D/B antagonist GR 127935 (50 nM). The preferential 5-HT1D agonist sumatriptan (0.5 microM) also decreased 5-HT efflux, to 55 +/- 6% and was antagonised by GR 127935 (50 nM) but not isamoltane (0.5 microM). These results suggest that 5-HT released in the vLGN can be measured by FCV. Furthermore, released 5-HT is taken up by the 5-HT transporter and may be under the influence of 5-HT1B and 5-HT1D autoreceptors.
 ...
PMID:Serotonin efflux in the rat ventral lateral geniculate nucleus assessed by fast cyclic voltammetry is modulated by 5-HT1B and 5-HT1D autoreceptors. 902 11