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

Serotonin (5-hydroxytryptamine; 5-HT) and its analogs activate adenylate cyclase in membrane particles from neuroblastoma NCB.20 cells. Low concentrations of GTP (EC50 = 60 nM) were required for activation by serotonin. Guanosine 5'-O-(2-thiodiphosphate) inhibited serotonin-activated cyclase in these cells. The nonhydrolyzable GTP analogs guanosine 5'-O-(3-thiotriphosphate) (EC50 = 3 nM) and guanylyl-imidodiphosphate (EC50 = 100 nM) substituted for GTP in potentiating serotonin activation. Pretreatment of the cells with cholera toxin potentiated enzyme activation by serotonin, whereas pertussis toxin was found to have little effect, indicating the involvement of the alpha subunit of a stimulatory GTP-binding protein in enzyme activation. Homologous desensitization of the serotonin-stimulated adenylate cyclase was demonstrated in membranes prepared from intact cells pretreated with serotonin. Cell membrane particles that were desensitized to serotonin were still responsive to beta-adrenergic agonists and to prostaglandin E1. Evidence is presented indicating that serotonin stimulation of adenylate cyclase is mediated by receptors that are distinct from other positively coupled receptors (beta-adrenergic, histamine, and prostacyclin). Equilibrium binding analysis with [3H]serotonin, [3H]lysergic acid diethylamide, and [3H]dihydroergotamine suggested that the site density was below the level of detection of binding of these radioligands. The pharmacological characteristics of the serotonin-activated cyclases were analyzed in order to compare these serotonin receptors with the family of different receptor subtypes. Correlation analysis between the potencies of different agonists and antagonists at the cyclase in these cells and their reported relative potencies for different serotonin receptor subtypes showed no correlation with the 5-HT1A, 5HT1B, 5HT1D, 5-HT2, and 5-HT3 receptors. On the other hand, the analysis showed that the NCB.20 serotonin receptors are similar but not identical to the rat and pig brain 5-HT1C receptors and to the serotonin receptors coupled to adenylate cyclase in the trematodes Schistosoma mansoni and Fasciola hepatica. The results point to a novel serotonin receptor which has a low density in these cells.
Mol Pharmacol 1990 May
PMID:Serotonin receptor-mediated activation of adenylate cyclase in the neuroblastoma NCB.20: a novel 5-hydroxytryptamine receptor. 233 46

Pulmonary endothelial extraction (E) of serotonin (5-HT) is decreased after exposure to phorbol myristate acetate (PMA) in intact (D. Riggs, A. M. Havill, B. R. Pitt, and C. N. Gillis. J. Appl. Physiol. 64: 2508-2516, 1988.) or perfused (C. L. Myers and B. R. Pitt. J. Appl. Physiol. 65: 377-384, 1988.) lungs. Although the mechanism underlying this change is unclear, we hypothesized, based on studies in cultured pulmonary arterial endothelial cells [C. L. Myers, J. S. Lazo, and B. R. Pitt. Am. J. Physiol. 258 (Lung Cell. Mol. Physiol. 1): L253-L258, 1989] that activation of protein kinase C (PKC) by PMA inhibits this uptake process. Accordingly, we studied the ability of staurosporine, a potent inhibitor of PKC, to block the acute effect of PMA on E(5-HT) by rat lungs perfused at 10 ml/min with Krebs-bicarbonate with 3% albumin. Pulmonary E(5-HT) was measured by indicator-dilution techniques using 5-[3H]HT and [14C]dextran. Both PMA and mezerein (nonphorbol PKC activator) caused dose-dependent decreases in E(5-HT) and increases in perfusion pressure (Ppa). Staurosporine, alone, did not significantly affect either E(5-HT) or Ppa; however, staurosporine (100 nM) completely inhibited the effects of PMA (100 nM) on the above parameters. Papaverine, a nonspecific vasodilator, was able to partially inhibit the pressor response to PMA while not affecting the inhibition of E(5-HT) by PMA, suggesting that the effect on E(5-HT) was not secondary to vasoconstriction (and derecruitment). These data support the hypothesis that activation of PKC leads to prominent pulmonary vascular effects including vasoconstriction and inhibition of endothelial cell 5-HT uptake.
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PMID:Activation of protein kinase C inhibits extraction of serotonin by perfused rat lung in situ. 236 Jun 42

Serotonin (5-HT)-induced stimulation or progesterone (P4) production by bovine luteal cells was characterized with respect to the receptor subtype mediating this response, the steroidogenic response to 5-HT metabolites, the role of adenylate cyclase, and the 5-HT concentration of bovine luteal tissue. Addition of 5-HT (10(-5) M) stimulated the production of P4 (P less than 0.05) and this stimulation was inhibited by the 5-HT antagonist mianserin at a concentration of 10(-5) M (P less than 0.05), but not at a mianserin concentration of 10(-7) M. Additionally, the response to 5-HT could not be inhibited by ketanserin (10(-5) M), a 5-HT2 receptor antagonist. Incubation of luteal cells with a specific 5-HT1 agonist, (+/-)-8-hydroxydipropylaminotetralin HBr (DPAT) (10(-4) M), stimulated the production of P4 (P less than 0.05) and this response could not be blocked by mianserin at 10(-7) M or by ketanserin, but was inhibited by mianserin at 10(-5) (P less than 0.05). The addition of the 5-HT metabolite 5-methoxytryptamine (5-MTA) stimulated P4 production (P less than 0.05) and this response could be inhibited by mianserin (10(-5) M, P less than 0.05). Neither, N-acetyl-5-HT nor 5-methoxytryptophan significantly affected P4 production. The addition of the phosphodiesterase inhibitor 3-isobutyl-methylxanthine (IBMX, 0.1 mM) potentiated the effects of 5-HT and DPAT (P less than 0.05), but this effect was additive rather than synergistic. In contrast, the addition of luteinizing hormone (10 ng/ml) plus IBMX resulted in a significant synergistic response (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1987 May
PMID:Mechanisms involved in the action of serotonin-induced stimulation of progesterone production by bovine luteal cells in vitro. 243 91

1. The effects of radiofrequency lesions of the ventral noradrenergic bundle (VNB) on monoamine and metabolite concentrations in several discrete areas of the rat hypothalamus were examined. Monoamines and metabolites were analyzed utilizing high-performance liquid chromatography coupled with electrochemical detection. 2. VNB lesions decreased the concentrations of norepinephrine (NE) and 3-methoxy-4-hydroxyphenylethylene glycol in all areas examined except in the ventromedial nucleus (VMN). Dopamine and 3,4-dihydroxyphenylacetic acid concentrations were selectively decreased in the dorsomedial nucleus (DMN) and also slightly decreased in the medial forebrain bundle following VNB lesions. Serotonin and 5-hydroxyindole-3-acetic acid concentrations were not altered by VNB lesion in any area examined. 3. The results indicate that the NE innervation to the hypothalamus is extensive and that NE in the VMN may not be derived from the VNB. The source of the DA innervation to the DMN may be located in or pass through the area affected by the VNB lesion.
Cell Mol Neurobiol 1987 Dec
PMID:Effect of ventral noradrenergic bundle lesions on concentrations of monoamine neurotransmitters and metabolites in several discrete areas of the rat brain. 245 60

Oocytes of the frog Xenopus laevis express various exogenous neurotransmitter receptors and ion channels when injected with RNA from excitable tissues. The oocytes serve as a convenient model system in which modulation of neurotransmitter responses can be studied. We examined the effects of activators and an inhibitor of protein kinase C (PKC) on responses to serotonin (5-HT), acetylcholine (ACh), kainate, and gamma-aminobutyric acid (GABA) in oocytes injected with RNA from rat brain. The PKC activators beta-phorbol esters 4 beta-phorbol-12-myristate-13-acetate (PMA) and 4 beta-phorbol-12,13-dibutyrate (PDBu), as well as the synthetic diacylglycerol, 1-oleyl-2-acetylglycerol (OAG), significantly inhibited the responses to 5-HT and ACh (both known to be mediated by mobilization of intracellular Ca2+); the first (transient) phase of these responses was affected stronger than the second, slow phase. PKC activators also reduced the response to GABA. The effect of PDBu on the response to kainate was dual; either inhibition or potentiation were observed at different concentrations of PDBu. The inactive analogue of PMA, the alpha-PMA, was without effect on the responses to 5-HT and GABA. The PKC inhibitor 1,5-isoquinolinesulfonyl-2-methylpiperazine (H7) suppressed the inhibitory effect of PDBu on 5-HT response. Amiloride, a blocker of the Na+/H+ exchange (which is known to be activated by PKC in some tissues), did not suppress the effects of PDBu. We concluded that activation of PKC down-regulates the responses to 5-HT, ACh and GABA, and has a dual effect on response to kainate. Possible mechanisms of these effects are discussed.
Brain Res Mol Brain Res 1989 May
PMID:Protein kinase C modulates neurotransmitter responses in Xenopus oocytes injected with rat brain RNA. 247 Oct 32

1. 3H-gamma-Aminobutyric acid (GABA) release elicited by a depolarizing K+ stimulus or by noradrenergic transmitter was examined in rat pineals in vitro. 2. The release of 3H-GABA was detectable at a 20 mM K+ concentration in medium and increased steadily up to 80 mM K+. 3. In a Ca2+-free medium 3H-GABA release elicited by 30 mM K+, but not that elicited by 50 mM K+, became blunted. 4. Norepinephrine (NE; 10(-6)-10(-4) M) stimulated 3H-GABA release from rat pineal explants in a dose-dependent manner. 5. The activity of 10(-5) M NE on pineal GABA release was suppressed by equimolecular amounts of prazosin or phentolamine (alpha 1- and alpha 1/alpha 2-adrenoceptor blockers, respectively) and was unaffected by propranolol (beta-adrenoceptor blocker). 6. The alpha 1-adrenoceptor agonist phenylephrine (10(-7)-10(-5) M) and the beta-adrenoceptor agonist isoproterenol (10(-5) M) mimicked the GABA releasing activity of NE, while 10(-7) M isoproterenol failed to affect it; the alpha 2-adrenoceptor agonist clonidine (10(-7)-10(-5) M) did not modify 3H-GABA release. 7. The addition of 10(-4) M GABA or of the GABA transaminase inhibitor gamma-acetylenic GABA or aminooxyacetic acid inhibited the melatonin content and/or release to the medium in rat pineal organotypic cultures. 8. GABA at concentrations of 10(-5) M or greater partially inhibited the NE-induced increase in melatonin production by pineal explants. 9. The depressant effect of GABA on melatonin production was inhibited by the GABA type A receptor antagonist bicuculline; bicuculline alone increased the pineal melatonin content. Baclofen, a GABA type B receptor agonist, did not affect the pineal melatonin content or release. 10. The decrease in serotonin (5-HT) content of rat pineal explants brought about by NE was not modified by GABA; GABA by itself increased 5-HT levels. 11. These results indicate that (a) GABA is released from rat pineals by a depolarizing stimulus of K+ through a mechanism which is partially Ca2+ dependent; (b) NE releases rat pineal GABA via interaction with alpha 1-adrenoceptors; (c) GABA inhibits melatonin production in vitro via interaction with GABA type A receptor sites; and (d) GABA's effect on NE-induced melatonin release does not correlate with the lack of effect on the NE-induced decrease in pineal 5-HT content.
Cell Mol Neurobiol 1989 Jun
PMID:Release and effect of gamma-aminobutyric acid (GABA) on rat pineal melatonin production in vitro. 247 90

1. The neuroblastoma x glioma hybrid NG108-15 cell line has been widely studied as a neuronal model for its serotonergic, cholinergic, and peptidergic properties. 2. The catecholamine and serotonin content and that of their major metabolites have been determined by high-performance liquid chromatography with electrochemical detection (HPLC-EC) in NG108-15 cells under differentiated and undifferentiated conditions. 3. Cellular contents of L-DOPA, norepinephrine, (NE), L-epinephrine (EPI), and dopamine (DA) in differentiated cells, induced by 1 mM dibutyryl cyclic AMP (dBcAMP), are 149, 40, 129, and 124%, respectively, higher than those in undifferentiated cells. 4. 3,4-Dihydroxyphenethylacetic acid (DOPAC), the major metabolite of DA, is detectable only in differentiated cells. Similarly, DOPAC is present only in culture medium from differentiated cells, and not that of undifferentiated cells. 5. Serotonin (5-HT) is detectable only in undifferentiated cells; and the level of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of 5-HT, is also 12.7% higher is undifferentiated cells. 6. Comparative analyses of differentiated and undifferentiated cells in monolayer cultures and undifferentiated cells cultured in the presence of 1 mM dBcAMP under suspension conditions suggest that change in the indolamine content is due to cellular changes upon morphological differentiation. 7. The clonal NG108-15 cell line is also catecholaminergic, in addition to cholinergic and serotonergic; and a shift of neurotransmitter pattern from serotonin to dopamine production occurs during morphological differentiation.
Cell Mol Neurobiol 1989 Sep
PMID:Modification of the indolamine content in neuroblastoma x glioma hybrid NG108-15 cells upon induced differentiation. 248 34

1. The procerebrum (PC) of the terrestrial slug Limax maximus is of interest as a potential site of olfactory information processing (Gelperin et al., 1989). The neuromodulator serotonin is present in the procerebrum and can elicit action potentials from cultured procerebral neurons. We have investigated the effects of serotonin on second-messenger signaling systems and protein phosphorylation as a prelude to studies on long-term synaptic plasticity in the Limax procerebral lobe. 2. We found that several biochemical changes are triggered within 20 min of adding serotonin to the isolated procerebral lobe: adenylate cyclase is activated, protein phosphorylation and synthesis are modulated, and phosphatidylinositol-metabolism is stimulated. 3. Serotonin causes a rapid synthesis of cAMP, reaching a 20- to 30-fold increase within 1 min. Serotonin affects the rate of phosphorylation of several proteins, detected after a brief (20-min) incubation of the procerebral lobe in [32P]phosphate-containing medium. The level of synthesis of several proteins is altered by serotonin, as determined by alterations in [35S]methionine incorporation during a 20-min incubation. Serotonin also causes a slow accumulation of inositoltrisphosphate. 4. Our study shows that within a short time (less than 20 min) serotonin can influence several second-messenger signaling systems and the functional state and abundance of proteins in the procerebral lobe. These serotonin-stimulated events should have direct consequences for intercellular communication in the odor-processing network of the procerebral lobe.
Cell Mol Neurobiol 1989 Dec
PMID:Serotonin-stimulated biochemical events in the procerebrum of Limax. 255 7

Endocrine cells were investigated in human Bartholin's glands by use of histochemical, immunohistochemical and ultrastructural methods. Endocrine cells represent normal constituents of these glands, being mainly distributed throughout the transitional epithelium of the major excretory duct; however, single elements are dispersed among the acinar lobules. Serotonin-, calcitonin-, katacalcin-, bombesin- and alpha-hCG-immunoreactive cells were recognized, with serotonin-immunoreactive cells predominating. Co-expression of calcitonin, katacalcin or alpha-hCG with serotonin was observed in single endocrine cells. At the ultrastructural level, these cells are richly granulated and show typical neuroendocrine features. Bartholin's glands display an endocrine profile quite similar to that of other cloacal-derived tissues.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Endocrine cells in human Bartholin's glands. An immunohistochemical and ultrastructural analysis. 256 49

Serotonin (5-hydroxytryptamine, 5-HT) receptors in the muscle and intestinal tissues of adult Ascaris suum have been investigated. [3H] lysergic acid diethylamide (LSD) exhibited specific and saturable binding to membranes prepared from both intestine and muscle. The intestinal tissue membranes had an equilibrium dissociation constant (Kd) of 2.70 nM for LSD and a Kd of 2.50 microM for 5-HT. As compared to the intestine, the muscle membranes had comparatively higher affinity for both LSD (Kd = 1.80 nM) and 5-HT (Kd = 0.68 microM). The muscle membranes also had a high binding affinity for ketanserin, a 5-HT2 antagonist, (Kd = 16.7 nM) whereas intestinal membranes exhibited no specific binding of ketanserin. Serotonin significantly inhibited the binding of LSD to the intestinal and muscle tissue membranes while adrenergic and cholinergic drugs and histamine did not. This suggested that the binding of LSD, 5-HT and ketanserin to the parasite membranes was specific. Collectively, the data demonstrated the presence of a serotonin receptor in the muscle and intestinal tissues of the adult A. suum. The receptor in the muscle was pharmacologically similar to the mammalian serotonin type 2 receptor.
Mol Biochem Parasitol 1989 Jul
PMID:Serotonin receptors in the tissues of adult Ascaris suum. 274 43


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