Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S-100 beta, a calcium binding protein produced by astrocytes, has been proposed to be a neuronotropic agent. In order to test the tropic effects of S-100 beta in vivo, the technique of cell transplantation was used. C6 glioma cells and C6 cells containing a S-100 beta antisense gene (C6AS) were transplanted into contralateral hippocampi. 5-HT immunoreactive, varicose fibers with a normal appearance penetrated into the glioma mass and were seen in high density around the C6 cell mass. However, 5-HT fibers with enlarged, abnormal varicosities were seen bordering C6AS tissue and were very rarely observed within the C6AS cell mass. Extracellular S-100 beta from normal C6 cells may function as a growth factor on sprouting serotonergic fibers.
Brain Res Mol Brain Res 1995 Apr
PMID:Serotonergic sprouting into transplanted C-6 gliomas is blocked by S-100 beta antisense gene. 760 24

Alterations in the catecholaminergic transmission during Newcastle disease virus (NDV) infection was studied in different brain regions of chick. The results obtained in the present study reveal that the epinephrine, norepinephrine, dopamine and 5-HT were decreased and monoamineoxidase activity was elevated during both the time periods of infection. The chickens after 72 h infection showed more depletion when compared to 24 h, indicating that the catecholaminergic activity was impaired during NDV infection.
Biochem Mol Biol Int 1995 May
PMID:Catecholaminergic transmission in different brain regions of chick during Newcastle disease virus (NDV) infection. 766 25

Glucocorticoids and serotonin (5-HT) modulate behaviour and hypothalamic-pituitary-adrenal (HPA) axis responses. The two systems interact prominently in the hippocampus, where these effects may occur. We have previously shown that hippocampal 5-HT2C receptor mRNA expression is increased by adrenalectomy or central 5-HT lesions. We have now determined expression of corticosteroid and 5-HT receptor subtype genes in the hippocampus across the diurnal cycle, when there are changes both in plasma corticosterone and hippocampal 5-HT levels, as well as the responses of these transcripts to acute and chronic stress, using in situ hybridisation histochemistry. Expression of both glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNAs was significantly higher (131-153%) in the hippocampus at 08.00 h (corticosterone nadir) than at 20.00 h (corticosterone peak). 5-HT2C receptor mRNA expression also showed circadian variation (106-184% higher in CA1-CA3 in the morning). Hippocampal 5-HT1A and 5-HT2A receptor mRNA expression had no diurnal variation. Chronic (15 day) adjuvant arthritis stress, abolished the circadian corticosterone nadir, maintaining plasma corticosterone around diurnal peak values. Chronic arthritis stress suppressed hippocampal 5-HT2C receptor mRNA expression at 08.00 h to levels comparable to 20.00 h controls. By contrast to chronic stress, 6 h after acute laparotomy stress, plasma corticosterone was elevated above control (20.00 h) and 5-HT2C receptor mRNA expression was increased (CA2). Neither acute nor chronic stress altered MR, GR, 5-HT1A or 5-HT2A receptor mRNA expression in any hippocampal subfield. These results show that hippocampal expression of the 5-HT2C receptor gene, but not other subtypes, is sensitive to a variety of manipulations.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1995 Feb
PMID:Modulation of serotonin and corticosteroid receptor gene expression in the rat hippocampus with circadian rhythm and stress. 772 17

The 5-hydroxytryptamine type 2 receptor gene is transcriptionally induced by 5-HT-mediated activation of the 5-HT2 receptor in rat myometrial smooth muscle cells. We recently cloned the promoter of the rat 5-HT2 receptor gene and showed that a 1.4-kilobase promoter construct transfected into myometrial smooth muscle cells displays both constitutive and serotonin-dependent promoter activity. We have examined a series of deletional mutants of this promoter for their transcriptional activity. Deletions from base pair (bp) -1314 to bp -184 (with respect to the major transcriptional start (site) resulted in no changes in constitutive or 5-HT-dependent transcriptional activity. A substantial loss of serotonin-dependent transcriptional activation was observed with a promoter construct from which the bp -184 to -108 sequence was deleted. A sequence [termed the serotonin-1 (S1) element], 5'-AGGTTnnnnnnnAACCT-3' (where n represents any deoxynucleotide), containing a novel dyad repeat is contained within this region. In addition to the S1 element, two simian virus 40 promoter factor 1 (SP-1) sites contiguous to this site, as well as an initiator element, appear to be important. Deletion of both the S1 and SP-1 sites resulted in an almost total loss of activity. Myometrial smooth muscle cells contain nuclear proteins that interact specifically with the S1 and SP-1 elements. Thus, multiple elements appear to be involved in serotonin-dependent induction of promoter activity. Analysis of the promoter elements that direct constitutive (i.e., serotonin-independent) activity revealed the involvement of a different region. Deletions from bp -1314 to bp -75 resulted in only minor increases in basal promoter activity. Deletion to bp -50 resulted in a 2.5-fold increase in basal promoter activity, whereas deletion to bp -25 resulted in a 5-fold increase in promoter activity. These results suggest that the basal promoter unit includes bp -25 to 1 and that upstream sequences act to repress basal promoter activity.
Mol Pharmacol 1995 May
PMID:Regulation of rat 5-hydroxytryptamine type 2 receptor gene activity: identification of cis elements that mediate basal and 5-hydroxytryptamine-dependent gene activation. 774 79

Due to the high level of expression of mRNA for the 5-hydroxytrytamine (5-ht7) receptor in the hypothalamus and the high affinity of 5-HT for this receptor, [3H]5-HT binding was performed in rat hypothalamus to determine whether 5-ht7 receptor binding sites are present in animal tissue. [3H]5-HT binding was performed in the presence of 100 nM pindolol, which is inactive at 5-ht7 receptors but prevents the binding of [3H]5-HT to 5-HT1A and 5-HT1B receptor binding sites. Under these conditions, [3H]5-HT bound to a binding site with an affinity of 1.94 nM. Displacement studies showed the pharmacology of the hypothalamic binding site to correlate well with the published pharmacology of the 5-ht7 receptor (r = 0.921). The treatment of rats with fluoxetine (5 mg/kg/day, orally) for 21 days caused a significant reduction in the number of hypothalamic 5-ht7 receptor binding sites. These data suggest that the 5-ht7 receptor binding site is expressed in rat hypothalamus and that this receptor binding site is down-regulated after a chronic increase in the synaptic level of 5-HT.
Mol Pharmacol 1995 Jan
PMID:Identification of 5-hydroxytryptamine7 receptor binding sites in rat hypothalamus: sensitivity to chronic antidepressant treatment. 783 38

These studies examined the contribution of serotonin (5-HT) to the control of prolactin (PRL) and vasoactive intestinal peptide (VIP) messenger RNA expression in rat anterior pituitary. Daily injection of rats with the biosynthetic precursor to serotonin, 5-hydroxytryptophan (5-HTP; 25 mg/kg, q.i.d.), resulted on day 5 in a 50% increase in the expression of PRL mRNA in the pituitary while at the same time reducing the levels of both the 1.0 and 1.7 kb VIP mRNA transcripts. Co-treatment of rats with 5-HTP plus the catecholamine biosynthesis inhibitor, alpha-methyl-tyrosine (alpha-MT; 150 mg/kg, q.d. x 2 days), or the dopamine receptor antagonist haloperidol (1.25 mg/kg, b.i.d. x 5 days), resulted in increases in pituitary PRL message levels that were greater than those observed with either anti-dopaminergic agent alone. In contrast, 5-HTP was unable to reverse the inhibition of PRL mRNA expression caused by treatment with the dopamine receptor agonist bromocriptine (2.5 mg/kg, b.i.d. x 5 days). Neither alpha-MT, haloperidol nor bromocriptine had a significant effect on pituitary VIP mRNA expression. Administration of the direct-acting 5-HT receptor agonist quipazine (5 mg/kg, b.i.d.) for 14 consecutive days caused a significant increase in pituitary PRL mRNA levels on day 1 and reached a plateau of 90% above control levels on days 7 and 14. VIP mRNA levels rose significantly on day 1 of quipazine treatment but thereafter fell to a minimum of 22% (1.0 kb) and 52% (1.7 kb) of control by day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Nov
PMID:Serotonergic involvement in the regulation of prolactin and vasoactive intestinal peptide mRNA expression in the rat anterior pituitary. 785 24

Glucocorticoid excess is associated with hippocampal neuronal dysfunction and loss, mainly affecting CA1. Degeneration of both cholinergic and serotonergic (5-HT) hippocampal afferents is prominent in aged rats and Alzheimer's disease. Lesions of these individual pathways alter hippocampal expression of mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNAs; both transcripts are increased by cholinergic lesions, but markedly decreased by serotonergic denervation. In the present study we found that combined medial septal cholinergic and central 5-HT lesions increase hippocampal GR mRNA expression, specifically in CA1 and CA2 subfields, whereas MR mRNA expression was similar to controls. Thus the effects of the cholinergic lesion, at least upon GR gene expression, appear to predominate while the effects of the lesions upon MR gene expression were additive. Increased hippocampal GR gene expression per neuron may increase hippocampal neuronal vulnerability with age or disease.
Brain Res Mol Brain Res 1994 Nov
PMID:Increased glucocorticoid receptor gene expression in the rat hippocampus following combined serotonergic and medial septal cholinergic lesions. 787 48

1. HIV gp120 selectively reduces the glutamate-induced inward current and the acetylcholine-induced outward current in specific and identified Aplysia neurons without affecting dopamine (DA)- and serotonin (5-HT)-induced responses. 2. gp120 specifically decreases DA levels without significantly altering norepinephrine and 5-HT levels in Mytilus pedal ganglia. 3. The gp120-associated decrease in DA levels in Mytilus is dose dependent and exhibits a threshold level. 4. The alteration of in vitro DA levels is specific for gp120 since anti-gp120 blocks the effect. 5. gp120 and its effects appear to be stable due to the duration of treatment and the failure of secondary effects to materialize following antibody treatment.
Cell Mol Neurobiol 1993 Dec
PMID:Selective effects of human immunodeficiency virus (HIV) gp120 on invertebrate neurons. 791 Jul 80

Tryptophan hydroxylase (TPH) catalyzes the first step of serotonin biosynthesis in serotonergic neurons and neuroendocrine cells. Serotonin influences diverse vital physiological functions and is thought to play an important role in several human psychiatric disorders. To localize DNA element(s) important for serotonergic tissue-specific expression of TPH, 6.1 kb of the 5' flanking region of the mouse TPH gene was fused to the coding region of the E. coli lacZ gene, and expression of the resulting fusion gene was analyzed in transgenic mice. The 6.1 kb of 5' flanking sequence was able to direct the expression of a lacZ reporter gene to serotonergic tissues in six lines of transgenic mice. A high level of lacZ expression in transgenic mice carrying the fusion gene was detected in the pineal gland as well as a moderate level of lacZ expression in serotonergic brain regions such as the median and dorsal raphe nuclei, the nuclei raphe magnus and raphe pallidus. In contrast, a smaller 5' flanking sequence of 1.1 kb directed no detectable serotonergic tissue-specific lacZ expression in five lines of transgenic mice. These results presented in this paper suggest first that DNA elements critical to serotonergic tissue-specific expression reside between -6.1 kb and -1.1 kb of 5' flanking region of the mouse TPH gene, but second that this region confers a restricted tissue-specific expression.
Brain Res Mol Brain Res 1994 Jul
PMID:A 6.1 kb 5' upstream region of the mouse tryptophan hydroxylase gene directs expression of E. coli lacZ to major serotonergic brain regions and pineal gland in transgenic mice. 796 51

The serotonin transporter (SERT) is a target for many clinically significant drugs, such as cocaine, amphetamine, and antidepressants. The relationship between the structure of SERT and the binding of substrates and antagonists is virtually unknown, despite a large body of data describing the structure-activity relationships of transporter ligands. The cloning of multiple species homologs of SERT affords a unique opportunity for molecular comparisons to identify potential domains and residues involved in ligand recognition. We have conducted pharmacological comparisons of the cloned rat and human SERTs in transiently transfected HeLa cells. Serotonin uptake and radioligand binding assays revealed that rat and human SERTs show different sensitivities to some but not all transporter ligands; most tricyclic antidepressants were significantly more potent at the human SERT, relative to rat SERT, whereas d-amphetamine was a more potent inhibitor of rat SERT. Several other ligand such as fluoxetine, paroxetine, (+)-methylenedioxymethamphetamine, cocaine, and the substrate 5-hydroxytryptamine, shows no significant species selectivity. Cross-species chimeras between rat and human SERTs were constructed to track the species-specific pharmacologies through the SERT molecule. These chimeric SERTs were expressed in HeLa cells and transported serotonin similarly to parental SERTs. Using these chimeras, we have isolated a region distal to amino acid 532 the imparts species preferences for both the tricyclic imipramine and d-amphetamine. Our results support the prediction of distinct binding sites for SERT ligands and implicate a restricted region in or near putative transmembrane domain 12 of the transport as being involved in both substrate and antagonist recognition.
Mol Pharmacol 1994 Nov
PMID:Chimeric human and rat serotonin transporters reveal domains involved in recognition of transporter ligands. 796 65


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