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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of the insect gland with [3H]inositol results in the incorporation of label into both phosphatidylinositol (PI) and the two polyphosphoinositides (PIP and PIP2). Upon stimulation with 5-HT the initial water-soluble metabolites released are inositol trisphosphate and inositol bisphosphate with no change in the level of inositol monophosphate, suggesting that the primary lipid substrate used by the receptor is one of the polyphosphoinositides (most likely PIP2) rather than PI. This conclusion was substantiated by showing that 5-HT was not able to release inositol or inositol monophosphate when the levels of the two polyphosphoinositides were reduced by lowering the level of ATP. The rate of breakdown of the polyphosphoinositides, as measured by the appearance of inositol phosphates, occurred with no apparent lag whereas the onset of the calcium-dependent change in transepithelial potential had a latency of approximately 1 sec. It is concluded that the primary action of 5-HT is to stimulate the hydrolysis of PIP2 into diacylglycerol and inositol trisphosphate. The latter may function as a second messenger to mobilize the calcium responsible for initiating some of the ionic events responsible for fluid secretion.
Mol Cell Endocrinol 1984 Jun
PMID:Relationship of polyphosphoinositide metabolism to the hormonal activation of the inset salivary gland by 5-hydroxytryptamine. 608 23

Adenylate cyclase of adult Schistosoma mansoni is activated by serotonin (5-hydroxytryptamine). Serotonin activation is markedly enhanced by GTP. the poorly hydrolyzed analogs of GTP, guanylyl imidophosphate (Gpp(NH)p) and guanosine 5' -(3-0-thio)triphosphate activate the schistosome cyclase in the absence of serotonin. The activating effect of these nucleotides is increased in the presence of serotonin. Female adult schistosomes have only 40% as much NaF-stimulated activity as do the male parasites. In addition, the serotonin stimulation of adenylate cyclase in the females is only 20% as much as the males. Maximal activation of adenylate cyclase with NaF reveals that the adult parasites have tenfold higher activity than the cercariae. cercarial adenylate cyclase shows very poor response to serotonin in the presence of GTP. Serotonin caused more significant activation of cercarial adenylate cyclase in the presence of guanylyl imidophosphate.
Mol Biochem Parasitol 1982 Feb
PMID:Adenylate cyclase in adults and cercariae of Schistosoma mansoni. 704 62

Neuroblastoma cells clone N-2a, differentiated by serum deprivation, were found to take up tritiated serotonin ([3H]5-HT) from the external medium by means of a saturable mechanism which follows Michaelis-Menten kinetics. The apparent Km of uptake was 1.27 microM and the Vmax 720 fmoles/min/10(6) cells. The uptake was temperature-dependent and partially sodium-dependent, and was inhibited by ouabain and by selected metabolic inhibitors (sodium azide, 2,4-dinitrophenol, and iodoacetamide). Fluoxetine and desmethylimipramine (DMI) were equally effective inhibitors of [3H]5-HT uptake (IC50 = 13.7 microM and 13.6 microM). The uptake was structurally specific, since unlabeled 5-HT was a better inhibitor of [3H]5-HT uptake than norepinephrine (NE) (IC 50 = 0.6 microM and 9.4 microM). The neurotoxins 6-hydroxydopamine and 5,6-dihydroxytryptamine were cytotoxic to differentiated N-2a cells, causing time- and concentration-dependent inhibition of [3H]thymidine incorporation into DNA, 5,7-Dihydroxytryptamine had little cytotoxic effect. Non-differentiated N-2a cells, supplemented with 5% fetal calf serum, were also found to take up [3H]5-HT by a concentration-, temperature-, and energy-dependent process. The apparent Km of uptake was 0.96 microM and the Vmax was 619 fmoles/min/10(6) cells. However, in nondifferentiated cells [3H]5-HT uptake was not sodium-dependent, not inhibited by ouabain, less effectively inhibited by fluoxetine and DMI (IC50 = 148 microM and 107 microM), and not selectively inhibited by unlabeled 5-HT as compared with NE (IC50 = 7.9 microM and 6.0 microM).
Mol Pharmacol 1982 Mar
PMID:Characterization of serotonin uptake in cultured neuroblastoma cells. Difference between differentiated and nondifferentiated cells. 709 39

PC-12 cells, derived from a rat pheochromocytoma, were found to take up tritiated serotonin ([3H]5-HT) from the external medium by means of a saturable mechanism which follows Michaelis-Menten kinetics. The apparent Km of uptake was 0.39 microM and the Vmax was 0.40 pmole/min/10(6) cells. The uptake was temperature-dependent, partially sodium-dependent, and inhibited by selected metabolic inhibitors (sodium azide, 2,4-dinitrophenol, and iodoacetamide), PC-12 cells also accumulated tritiated norepinephrine ([3H]NE) by a saturable process, with an apparent Km of 1.13 microM and a Vmax of 1.72 pmole/min/10(6) cells. This NE uptake process was also temperature- and sodium-dependent and inhibited by metabolic inhibitors and ouabain. Desmethylimipramine (DMI, IC50 = 3.8 microM) was a better inhibitor of [3H]NE uptake than fluoxetine (IC50 = 24.6 microM). The NE uptake process was structurally specific, since unlabeled NE was a better inhibitor of [3H]NE uptake than 5-HT (IC50 = 19.6 and 171 microM, respectively). However, [3H]5-HT uptake in PC-12 cells appeared to be a less structurally specific process, as it was equally inhibited by unlabeled 5-HT and NE (IC50 4.9 microM and 4.3 microM, respectively). DMI was also a better inhibitor of [3H]5-HT uptake than fluoxetine (IC50 = 85 and 411 microM, respectively). The neurotoxins 6-hydroxydopamine and 5,6-dihydroxytryptamine were cytotoxic to PC-12 cells, causing a time- and concentration-dependent inhibition of [3H]thymidine incorporation into DNA. 5,7-Dihydroxytryptamine had little cytotoxic effect toward PC-12 cells in culture.
Mol Pharmacol 1982 Mar
PMID:Characterization of serotonin uptake in cultured pheochromocytoma cells. Comparison with norepinephrine uptake. 709 40

Glucose uptake by Hymenolepis diminuta was linear for up to 60 min following in vitro incubation in 10 mM glucose. Following the addition of 1 mM 5-HT, with a 95% O2/5% CO2, gas phase, glucose uptake by H. diminuta was significantly (P less than 0.001) enhanced, remaining linear and parallel to that of control groups between 15 and 60 min incubation. Under air, the rates of glucose uptake were higher, but were only significantly increased by 5-HT during the first 30 min of incubation. In further experiments, in the absence of glucose in the incubation media worm glycogen reserves decreased by over 50% after 60 min. With the addition of 1 mM 5-HT, the reduction in glycogen content was significantly (P less than 0.025) greater, exceeding 65% after 60min. When glucose was added to the incubation media, worm glycogen reserves were not significantly depleted irrespective of the presence or absence of 5-HT. Incubations under a 95% O2/5% CO2 gas phase did not significantly influence glycogen content compared to corresponding groups incubated in air. The results suggest that 5-HT stimulates glycolysis in H. diminuta through increased glucose uptake by the worm or by a reduction in glycogen reserves in the absence of external glucose.
Mol Biochem Parasitol 1981 Dec
PMID:Effect of 5-hydroxytryptamine (5-HT; serotonin) on in vitro glucose uptake and glycogen reserves in Hymenolepis diminuta. 732 43

It is known that long-term treatment with antidepressants induces an enhancement of neurotransmission in the pathway projecting from raphe nuclei to the hippocampus. In the case of selective serotonin (5-HT) reuptake inhibitors, this enhancement is due to a desensitization of presynaptic 5-HT autoreceptors and a concomitant increase in 5-HT release in terminal areas. To investigate whether this effect is accompanied by adaptive changes in the molecular machinery regulating transmitter release at serotonergic terminals, autophosphorylation and activity of Ca2+/calmodulin-dependent protein kinase II were measured in subsynaptosomal fractions from hippocampus and total cortex. Long-term treatment with two selective serotonin reuptake inhibitors (paroxetine and fluvoxamine) and with a nonselective reuptake inhibitor (venlafaxine) induces a large increase of kinase autophosphorylation in synaptic vesicles and synaptic cytosol in the hippocampus but not in synaptosomal membranes. No significant change was detected in total cortex. The change is not reproduced by the direct addition of the drugs to the phosphorylation system and is not elicited by acute treatment of the animals. The increase in autophosphorylation is not accounted for by neosynthesis or translocation of the kinase to synaptic terminals. The change is restricted to the kinase located inside the terminals and is not detected in synaptosomal membranes, containing predominantly postsynaptic kinase, suggesting that only presynaptic kinase is affected. In the same fractions, the kinase activity is increased. These results are in agreement with reports suggesting a presynaptic effect for the SSRIs and disclose a new putative site of action for psychotropic drugs.
Mol Pharmacol 1995 Oct
PMID:Presynaptic Ca2+/calmodulin-dependent protein kinase II: autophosphorylation and activity increase in the hippocampus after long-term blockade of serotonin reuptake. 747 87

Since its discovery, serotonin (5-hydroxytryptamine = 5-HT) has become a major player on the neurotransmitter "stage". Multiple receptor subtypes for 5-HT have been identified and classified, and a vast pharmacology of 5-HT has emerged. In particular, 5-HT has been shown to exert marked effects on the cardiovascular system, central nervous system (CNS) and gastrointestinal (GI) tract, and important ligands have been developed that mimic or block its action selectively. Furthermore, drugs that release 5-HT, and others that prevent its uptake, have been developed. This brief review focuses on the pharmacology of 5-HT agonists and antagonists that exhibit, at least partly, clinical relevance.
Cell Mol Biol (Noisy-le-grand) 1994 May
PMID:Serotonin receptors and therapeutics. 752 16

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.
Mol Pharmacol 1995 Mar
PMID:Nonopioid mechanism of morphine modulation of the activation of 5-hydroxytryptamine type 3 receptors. 753 78

We have explored the possible involvement of the phosphoinositide (PI) cycle and protein kinase C (PKC) in the phytochrome (Pfr)-mediated light signal transduction pathway using nitrate reductase (NR) and phytochrome-I (PhyI) genes as model systems. We have shown earlier that phorbol myristate acetate (PMA) completely replaces the red light effect in stimulating nitrate reductase activity and transcript levels in maize. In this paper, we present detailed evidence to show that PMA mimics the red light effect and follows similar kinetics to enhance NR steady-state transcript accumulation in a nitrate-dependent manner. We also show that PMA inhibits phyI steady-state transcript accumulation in a manner similar to red light, indicating that a PKC-type enzyme(s) may be involved in mediating the light effect in both cases. Serotonin or 5-hydroxytryptamine (5-HT), a stimulator of PI turnover, was also found to mimic the red light effect in enhancing NR transcript levels and inhibiting phyI transcript accumulation, indicating the role of the PI cycle in generating second messengers for regulating the two genes. These results indicate that phytochrome-mediated light regulation of NR and phyI gene expression may involve certain common steps in the signal transduction pathway such as the PI cycle and protein phosphorylation by a PKC-type enzyme.
Plant Mol Biol 1995 Oct
PMID:Evidence for some common signal transduction events for opposite regulation of nitrate reductase and phytochrome-I gene expression by light. 757 65

Neuronal activity of the suprachiasmatic nucleus (SCN) is known to be regulated by two major extrinsic factors conveyed by three anatomically distinct pathways to the SCN: photic stimulus by the direct retinohypothalamic tract (RHT) and the indirect geniculohypothalamic tract (GHT), and information from the brainstem by ascending forebrain serotonergic (5-hydroxytryptamine: 5-HT) tract. It has been shown that VIP mRNA level in neurons of the SCN is altered by external light, but remains stable in constant darkness. In the present study, by using the in situ hybridization technique combined with computer-assisted image analysis, we examined VIP mRNA expression in the SCN of rats in which the two major factors were eliminated, i.e. photic stimulus by exposing animals in total darkness and 5-HT transmission by three-day successive administration of p-chlorophenyl-alanine methylester (an inhibitor of tryptophan hydroxylase, 200 mg/kg, daily). In saline-treated controls, VIP mRNA levels remained almost constant throughout the day. In contrast, in PCPA-treated rats, a significant rhythm of VIP mRNA was observed with a peak at CT 4 and a trough at CT 20. These observations suggest that the removal of photic and 5-HT influence induces VIP mRNA rhythm in the SCN, indicating that VIP mRNA is controlled not only by photic information but also by the circadian clock.
Brain Res Mol Brain Res 1995 Apr
PMID:Circadian change of VIP mRNA in the rat suprachiasmatic nucleus following p-chlorophenylalanine (PCPA) treatment in constant darkness. 760 23


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