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)

1. Reserpine (5 mg/kg intraperitoneally) produced gastric mucosal vasoconstriction and injury in all rats within 6 h (injury score 38.8 +/- 2.1 mm2, mean +/- SEM). Coeliac ganglionectomy or the beta-adrenoceptor-blocking drug propranolol (5-15 mg/kg) did not influence these effects of reserpine, but vagotomy protected the rats against them. The alpha-adrenoceptor-blocking drugs phenoxybenzamine and phentolamine at 5 mg/kg were protective against injury. However, a 10 mg/kg dose of either blocker was more effective (2.2 +/- 0.5 mm2 and 3 +/- 0.8 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM, P less than 0.01) and a dose of 15 mg/kg afforded complete protection. 2. Methysergide, a 5-hydroxytryptamine receptor antagonist, produced a dose-dependent increase in the reserpine-induced injury; a significant (P less than 0.05) increase was noted with 15 and 20 mg/kg (47.5 +/- 2.9 mm2 and 49.4 +/- 2.2 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM). 3. The results suggest that, in the rat, reserpine causes vagal alpha-adrenoceptor stimulation producing gastric mucosal vasoconstriction and injury. 5-Hydroxytryptamine is not implicated in the mechanism of this injury and affords protection against it.
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PMID:Mechanism of reserpine-induced acute gastric mucosal injury in the rat: role of endogenous 5-hydroxytryptamine. 184 92

[3H]A-69024 has been prepared as a radioligand for studying the dopamine D1 receptor. [3H]A-69024 binds to rat striatal membranes with a KD = 14.3 +/- 3.2 nM (mean +/- SEM; n = 3) and Bmax = 63.5 +/- 12.8 fmol/mg wet tissue (1.8 +/- 0.3 pmol/mg protein). This ligand binds to only one site with a Hill coefficient close to unity. The in vivo biodistribution of [3H]A-69024 showed a high uptake in the striatum (5.9% ID/g) at 5 min followed by clearance. As a measure of specificity, the striatum/cerebellar ratio reached a maximum of 6.7 at 30 min post-injection. Pre-treatment with the D1 antagonist R(+)SCH 23390 (1 mg/kg) reduced this ratio to unity. The dopamine antagonist (+)butaclamol and unlabeled A-69024 inhibited striatal uptake by 70 and 51%, respectively. Spiperone (D2/5-HT2A) and ketanserin (5-HT2A/5-HT2C) at doses of 1 mg/kg had no inhibitory effect on [3H]A-69024 uptake in the striatum; however, increased uptake of [3H]A-69024 by > 30% in the whole brain was observed. The selectivity and affinity of [3H]A-69024 suggests that this non-benzazepine radioligand may be useful for in vitro and in vivo studies of the dopamine D1 receptor.
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PMID:[3H]A-69024: a non-benzazepine ligand for in vitro and in vivo studies of dopamine D1 receptors. 747 60

Participation of central 5HT receptors in the inhibition of LH pulsatility during refractoriness to short days (SD) in ewes has been suggested by previous in vivo studies using various 5HT-antagonist such as ketanserin. In the present study, binding of [3H]ketanserin in ewe brain sections was similar to that described in the brain of other species and could correspond with an interaction at 5HT2 receptors sites. Rosenthal analysis from the caudate nucleus was linear (Kd = 3 nM). The displacement studies from the cortex slices showed that the 5HT antagonists such as methysergide, ketanserin, cyproheptadine and spiperone competed with the labelled ligand at nanomolar concentrations whereas serotonin was less active. However, the first 3 drugs recognized different populations of binding sites. Prazosin, an alpha 1-adrenergic antagonist was inactive, but a slight inhibition of [3H]ketanserin binding was induced by pyrilamine, an H1 histaminic antagonist, within a nanomolar range. Methysergide (10(-6) M), which does not bind to H1 receptors, was therefore used to determine the nonspecific binding. Quantitative analysis of the binding of 3 nM [3H]ketanserin on sections of the ewe brain at the preopticohypothalamic level was then carried out by autoradiography. The highest binding densities were observed in the caudate nuclei (64.0 fmol/mg tissue Eq) and the mammillary bodies (52.7 fmol/mg tissue Eq) whereas intermediate or low densities were found in the other structures. The anatomical distribution of the labelling was similar to that described in other species for 5HT2 receptors. Ketanserin binding in these areas was compared between two groups of ovariectomized estradiol-treated Ile-de-France ewes, submitted to artificial short days (SD: 8L:16D), one group with a high LH pulsatility (responsive to SD) and the other one with a low LH pulsatility (photorefractory to SD). Binding densities were similar for each one of the studied regions between the two groups, except in the ventrolateral part of the mediobasal hypothalamus, where ewes exhibiting high LH pulsatility had a more than 2-fold higher binding density than those with a low LH pulsatility (mean +/- SEM, 14.6 +/- 1.4 vs. 5.7 +/- 1.0 fmol/mg tissue Eq, respectively; p < 0.0016). These results suggest that [3H]ketanserin binding sites in the ventromedial part of the mediobasal hypothalamus could be associated to the regulation of the photoperiodic inhibition of LH at the time of establishment of refractoriness to short days in the Ile-de-France ewe.
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PMID:Differences in ketanserin binding in the ventromedial hypothalamus of ewes responsive or refractory to short days. 770 May 2

Previous studies with high doses of cyproheptadine suggested that serotonergic (5HT) neural mechanisms participate in the photoperiodic inhibition of secretion of LH in ovariectomized estradiol-treated ewes. In the present study, we tested this hypothesis further with lower doses of more specific 5HT2 receptor antagonists, including the highly specific ketanserin. Eight ovariectomized estradiol-treated ewes were subjected to 90 long days (16L:8D) followed by 207 short days (8L:16D) in order to induce photorefractoriness. Plasma LH concentrations were measured in blood sampled twice weekly. Changes in LH pulse frequency were measured after intrajugular injections of cyproheptadine or ketanserin (0.1, 0.25, 0.6, and 1.5 mg/kg) before the increase in LH secretion induced by the short days (SD ewes). After the ewes became refractory to short days (RSD ewes), they were again treated with the three lowest doses of cyproheptadine and ketanserin and, in addition, methysergide at the same doses. In the period following the transition from long to short photoperiod, LH secretion increased above basal levels after 42.0 +/- 0.0 days (mean +/- SEM) and then decreased after 137.0 +/- 7.4 days. In SD ewes, cyproheptadine significantly increased the number of LH pulses at the lowest dose tested (0.13 vs. 1.13 pulses/3 h at 0.1 mg/kg). Similar responses were observed at 0.25 mg/kg (0.13 vs. 0.88 pulses/3 h), at 0.6 mg/kg (0.13 vs. 0.75 pulses/3 h) and at 1.5 mg/kg (0.13 vs. 0.88 pulses/3 h). Ketanserin induced a dose-dependent increase in the number of LH pulses at 0.6 mg/kg (0 vs. 0.63 pulses/3 h) and at 1.5 mg/kg (0 vs. 0.75 pulses/3 h).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonergic 5HT2 receptors mediate the inhibitory action of serotonin on luteinizing hormone secretion in ovariectomized, estradiol-treated ewes that are refractory to short days. 835 80

Recent head-twitch response (HTR) studies in mice have indicated that withdrawal from chronic cocaine exposure produces deficits in CNS conversion of L-tryptophan to 5-HT. In the present study, the ability of 5-HT releaser, d-fenfluramine, was utilized to induce the HTR in mice following abstinence from chronic cocaine exposure. d-Fenfluramine-induced HTR, is a 5-HT2A receptor-mediated phenomenon and its induction frequency can be regarded as an indirect but in vivo measure of basal brain 5-HT concentration. Thus, different groups of mice were injected with cocaine twice daily (0, 0.1, 0.5, 2.5, 5 or 10 mg/kg, i.p.) for either 7 or 13 days. At 24 h after last cocaine injection, the treated mice received d-fenfluramine (5 mg/kg, i.p.) and the induced HTR (mean+/-SEM) was recorded for the next 30 min. Cocaine attenuated the d-fenfluramine-induced HTR frequency by 30-37% in the 13-day regimen and significant effects were observed from 0.5 mg/kg dose. At 24 h withdrawal in the 7-day cocaine exposure group, the mean HTR frequencies were attenuated, however, they did not achieve statistical significance. Extended abstinence studies (i.e. 24, 48, 72 and 96 h postwithdrawal) from chronic cocaine exposure (0, 0.5 and 5 mg/kg/day for either 7 or 13 days) indicated that in the 7-day exposure group, significant reductions (26, 39 and 22%) in HTR frequency occurred at 48, 72 and 96 h following withdrawal from 0.5 mg/kg cocaine, whereas its 5 mg/kg dose failed to induce a significant effect. In the 13-day exposure group significant reductions in HTR frequency were observed at 24 h abstinence (27%) for the 0.5 mg/kg cocaine dose and at 24 and 48 h for the 5 mg/kg. Overall, these results indicate that abstinence from chronic exposure to cocaine produces enduring deficits in basal 5-HT concentration. Lastly, serotonergic function appears to be uniquely sensitive to chronic administration of low doses of cocaine.
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PMID:Deficits in D-fenfluramine-sensitive pool of brain 5-HT following withdrawal from chronic cocaine exposure. 941 80

This report investigated whether postnatal exposure to cocaine affects the index of 5-HT2A receptor function during development by utilizing the ability of the 5-HT2A/C agonist DOI to induce the head-twitch response (HTR) in mice. Thus, several groups of mice litters were treated with varying doses of cocaine (0, 0.5, 1, 5, and 10 mg/kg, IP) twice daily from postnatal days 5 to 14. Then, different groups of cocaine-exposed male mice pups along with their corresponding age-matched vehicle-exposed control groups were HTR tested once during development on the following postnatal test days: 15, 16, 18, 20, 30, 45, and 60. The HTR testing involved administration of DOI (0.5 mg/kg, IP) and counting the frequency of the behavior for the next 20 min. Cocaine exposure caused bell-shaped, dose-dependent, enduring but reversible increase in DOI-induced HTR frequency (mean +/- SEM) during development. The developing pups were most sensitive to low and intermediate doses of cocaine (0.5-5 mg/kg). The greatest degree of increase in HTR frequency in response to DOI challenge occurred in the 1 mg/kg cocaine-exposure group on most test days. The onset of HTR supersensitivity varied from 48 h (5 mg/kg) to 144 h (0.5 mg/kg) following the termination of chronic cocaine exposure. Moreover, maximal supersensitivity for the latter doses of cocaine occurred 96 and 384 h postcocaine treatment, respectively. Other cocaine exposure groups attained their maxima sometime between the latter time periods. The duration of persistence of 5-HT2A receptor supersensitivity varied with different doses of cocaine: the 10-mg/kg group was supersensitive up to 384 h postcocaine treatment, the 1- and 5-mg/kg groups up to 744 h; and the 0.5-mg/kg group up to 1104 h. Although developmentally cocaine-exposed pups exhibit some similarities (i.e., exquisite sensitivity and bell-shaped dose-response) in 5-HT2A receptor adaptation to mature adult mice exposed to cocaine, they also differ from mature adult cocaine-exposed mice in the onset of appearance as well as the enduring persistence of the induced supersensitivity.
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PMID:Early postnatal cocaine exposure causes sequential, dose-dependent, enduring but reversible supersensitivity in 5-HT2A receptor-mediated function during development in male mice. 1064 15