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1.
The possibility that an increased intracellular concentration of cyclic AMP (cAMP) can regulate the extent of muscarinic receptor-stimulated phosphoinositide (PPI) turnover in the human neuroblastoma cell line SK-N-SH was examined. Addition of either forskolin (or its water-soluble analog, L-85,8051), theophylline, isobutylmethylxanthine, or cholera toxin, agents that interact with either the catalytic unit of adenylate cyclase, cAMP phosphodiesterase, or the guanine nucleotide binding protein linked to adenylate cyclase activation, resulted in a 45-181% increase in cAMP concentration and a 27-70% inhibition of carbachol-stimulated inositol phosphate release. Through the use of digitonin-permeabilized cells, the site of inhibition was localized to a step at, or distal to, the guanine nucleotide binding protein that regulates phospholipase C activity. In contrast, when intact SK-N-SH cells were exposed to prostaglandin E1, the ensuing increases in cAMP were not accompanied by an inhibition of stimulated PPI turnover. These differential effects of increased cAMP concentrations on stimulated PPI turnover may reflect the compartmentation of cAMP within SK-N-SH cells. 相似文献
2.
Differentiation of Human Neuroblastoma Cells: Marked Potentiation of Prostaglandin E-Stimulated Accumulation of Cyclic AMP by Retinoic Acid 总被引:2,自引:2,他引:2
Victor C. Yu‡ Güinther Hochhaus Fu-Hsiung Chang† Mark L. Richards Henry R. Bourne † Wolfgang Sadée 《Journal of neurochemistry》1988,51(6):1892-1899
Neuroblastoma cells in culture contain low levels of cyclic AMP, a second messenger which plays a major role in neuronal maturation. In this study, human neuroblastoma cells, SK-N-SH-SY5Y, were induced to differentiate by treatment with either nerve growth factor (50 ng/ml), retinoic acid (10 microM), dibutyryl cyclic AMP (1 mM), or 12-O-tetradecanoylphorbol-13-acetate (0.1 microM), and the ability of several neurotransmitters or hormones to stimulate adenylyl cyclase was tested. Although all four differentiation factors caused morphological changes towards a neuronal phenotype, only retinoic acid dramatically enhanced cyclic AMP accumulation, specifically upon stimulation with prostaglandin E1 (PGE1). PGE2 was also active, but less potent, than PGE1, whereas the other cyclic AMP-stimulating agents tested were largely unaffected. Further, the rapid desensitization of the PGE1-cyclic AMP response observed in control cells after 20 min of PGE1 exposure did not occur in retinoic acid-treated cells, and the EC50 values for PGE1 were reduced from approximately 240 to 14 nM after retinoic acid treatment. The increased sensitivity to PGE was associated with an increase of high-affinity PGE1 binding sites, whereas the Gs coupling proteins and adenylyl cyclase were not measurably affected. A similar enhancement of the PGE1-cyclic AMP response by retinoic acid was also observed in two additional human neuroblastoma cell lines tested, Kelly and IMR-32, suggesting that up-regulation of the prostaglandin response by retinoic acid is common among neuroblastoma cells.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
Differential Regulation by Butyrate and Dibutyryl Cyclic AMP of δ-Opioid, α2 -Adrenergic, and Muscarinic Cholinergic Receptors in NCB-20 Cells 总被引:1,自引:1,他引:1
Long-term treatment of NCB-20 cells with sodium butyrate resulted in a marked increase in the specific binding of [3H]D-Ala2,D-Leu5 enkephalin. This increase was concentration and time dependent, with an EC50 of about 480 microM and a maximal effect detected after 3-day treatment. At saturating concentration of butyrate (1 mM) the increase was three- to fourfold of the untreated control. Scatchard analysis revealed that the butyrate effect was due to an increase in the density of the opioid receptor binding sites. Butyrate also induced a smaller (about twofold) increase in the density of muscarinic cholinergic receptor binding assessed by using [3H]quinuclidinyl benzilate, whereas alpha 2-adrenergic receptor binding assessed by using [3H]clonidine was not significantly affected. The butyrate-induced opioid receptor binding could be totally abolished by the presence of cycloheximide, suggesting that the butyrate effect involves synthesis of the receptor protein. Butyrate treatment did not affect basal and prostaglandin E1-stimulated cyclic AMP levels but caused a three- to fourfold decrease in the IC50 of D-Ala2,D-Leu5 enkephalin for attenuating these cyclic AMP levels and approximately 25% increase in the maximal extent of attenuation. In contrast to the butyrate effect, long-term treatment of NCB-20 cells with 1 mM dibutyryl cyclic AMP induced an 80% decrease in the opioid and alpha 2-adrenergic receptor bindings and a 57% loss of muscarinic cholinergic receptor binding. This down-regulation of muscarinic cholinergic receptor binding sites was associated with a 35% decrease of carbachol-induced phosphoinositide breakdown, whereas the receptor up-regulation induced by butyrate was found to increase the carbachol response by about threefold. The differential regulation by butyrate and dibutyryl cyclic AMP suggests that the butyrate effect is mediated by a mechanism independent of intracellular cyclic AMP. The induction by butyrate of opioid-receptors and muscarinic cholinergic receptors in NCB-20 cells may provide a useful system for studying the regulation of gene expression of these receptor proteins. 相似文献
4.
Abstract: Nerve growth factor (NGF) and dibutyryl cyclic AMP (dbcAMP) have synergistic effects on the neurite outgrowth of rat pheochromocytoma PC12 cells. The sites of interaction between NGF and dbcAMP have been studied extensively; however, the role of Ca2+ in differentiation induced by the two agents remains unclear. To understand whether intracellular Ca2+ is involved in the differentiation induced by the two agents, PC12 cells were treated with NGF, dbcAMP, or NGF plus dbcAMP for 2 days, and then effects on neurite outgrowth, ATP-induced Ca2+ influx, and Ca2+ mobilization from intracellular Ca2+ pools were examined. NGF or dbcAMP alone enhanced neurite outgrowth and Ca2+ accumulation by nonmitochondrial Ca2+ pools or the thapsigargin (TG)-sensitive Ca2+ pool. The dbcAMP acted synergistically with NGF to increase neurite outgrowth and to enlarge the TG-sensitive Ca2+ pool. The synergistic effect occurred within the first hour of treatment with dbcAMP plus NGF. On the other hand, dbcAMP abolished NGF's ability to enhance ATP-induced influx of extracellular Ca2+ . Therefore, NGF and dbcAMP induced different effects on Ca2+ signaling pathways through two different but interacting pathways. In PC12 cells pretreated with TG to deplete the TG-sensitive Ca2+ pool, the dbcAMP- or dbcAMP plus NGF-mediated neurite outgrowth was significantly inhibited, whereas NGF-mediated neurite outgrowth was not affected by TG pretreatment. Our results suggest that the intracellular nonmitochondrial Ca2+ pools were changed in the differentiation process and were necessary for the synergistic effect of NGF and dbcAMP. 相似文献
5.
Regulation of Glycerol Phosphate Dehydrogenase and Lactate Dehydrogenase Activity by Forskolin and Dibutyryl Cyclic AMP in the C6 Glial Cells 总被引:1,自引:2,他引:1
We have compared the effects of norepinephrine, forskolin, and dibutyryl cyclic AMP (Bt2cAMP) on the regulation of the cytosolic enzyme glycerol phosphate dehydrogenase (GPDH) in the C6 rat glioma cell line. Forskolin and Bt2cAMP elicit a dose-dependent increase in the levels of the enzyme that was, however, unaffected by norepinephrine. The half-maximal effect of forskolin was obtained at 7-8 microM, and the effect was maximal at 30 microM. Dexamethasone at a 50 nM concentration produced a two- to sixfold induction of GPDH after 48 h. The combination of dexamethasone with forskolin or Bt2cAMP leads to an elevation in GPDH levels that is higher than that produced by one of the compounds alone. This potentiation is found when both agents are added together with or after the glucocorticoid. The increase in uninduced and dexamethasone-induced GPDH activity was blocked by cycloheximide and actinomycin D, indicating that de novo protein and RNA synthesis are required. The activity of cytosolic lactate dehydrogenase activity did not change after incubation with dexamethasone, but increased with forskolin or Bt2cAMP. 相似文献
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7.
Effects of Dibutyryl Cyclic AMP and Retinoic Acid on the Differentiation of Dopamine Neurons: Prevention of Cell Death by Dibutyryl Cyclic AMP 总被引:2,自引:0,他引:2
Maria Angeles Mena Maria José Casarejos Ana Bonin Jose Antonio Ramos †Justo García de Yébenes 《Journal of neurochemistry》1995,65(6):2612-2620
Abstract: Immature neurons, including fetal and tumoral cells, are used for investigating neuronal differentiation in vitro. The human neuroblastoma cell line NB69 could be induced to differentiate to dopamine or acetylcholine neurons by different compounds, including neurotrophins and activators of the protein kinases. In these NB69 cells dibutyryl cyclic AMP (dbcAMP) at 2 m M reduced the division rate and increased the levels of catecholamines, tyrosine hydroxylase (TH) activity, and monoamine oxidase activity. The dbcAMP also increased cell size, dendritic arborization, density of the sites for high-affinity dopamine uptake, and activity of choline acetyltransferase. In fetal rat midbrain neurons treatment with dbcAMP increased the levels of dopamine and the number of TH-immunoreactive neurons in the culture. When embryonic day 14 fetal midbrain neurons, previously exposed to 1 µ M retinoic acid (a compound that severely reduces the number of fetal midbrain dopamine neurons), were treated with dbcAMP, the levels of dopamine and the number of TH-immunoreactive cells returned to normal levels. This suggests that dbcAMP induces the differentiation to dopamine neurons of quiescent progenitor or facilitates expression of the dopamine phenotype in immature neurons. Therefore, dbcAMP not only differentiates uncommitted immature dopamine neurons, but also reverses the antidopaminergic effects of retinoic acid. These properties of dbcAMP could be of therapeutic value in Parkinson's disease. 相似文献
8.
The increase in hormone-stimulated cyclic AMP accumulation observed in a variety of intact cells after chronic pretreatment with drugs that inhibit adenylate cyclase activity has been attributed to an increase in adenylate cyclase activity following withdrawal of the inhibitory drug. In NG 108-15 mouse neuroblastoma X rat glioma hybrid cells (NG cells) chronically treated with the muscarinic cholinergic agonist carbachol, we have found a significant decrease in the apparent degradation rate constant for cyclic AMP, in addition to an increase in the prostaglandin E1 (PGE1)-stimulated cyclic AMP synthesis rate in intact cells. In carbachol-pretreated NG cells that were stimulated with a maximally effective dose of PGE1, and that accumulated steady-state cyclic AMP concentrations fourfold or more higher than in control cells, the apparent rate constant for degradation was about 53% lower than the value for control cells. In carbachol-pretreated cells stimulated with a submaximal dose of PGE1 to yield a steady-state cyclic AMP concentration comparable to control cells, the apparent rate constant was 31% lower than the value for control cells. In S49 mouse lymphoma cells (S49 cells) chronically treated with an analog of the inhibitory agonist somatostatin, the first-order rate constant for cyclic AMP degradation in intact cells following isoproterenol stimulation was 29% lower than the value for control cells. Despite these changes in the kinetics of cyclic AMP degradation in intact NG cells and S49 cells, there was either no change or a minimal change (less than 10%) in phosphodiesterase activities assayed in extracts of cells chronically exposed to inhibitory drugs.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
Abstract: Tyrosine hydroxylase (TH) activity is increased two- to threefold in neuroblastoma cell line NBP2 maintained in culture for 48 h in the presence of either the inhibitor of cyclic AMP-phosphodiesterase (PDE), 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20- 1724), or the activator of adenylate cyclase, prostaglandin E1 (PGE1). Cyclic AMP levels are elevated 70–80% and 30–40% throughout the 48-h treatment with RO 20-1724 and PGE1, respectively. Carbachol does not affect either basal TH activity or cyclic AMP levels in the cells. However, the cholinergic agonist delays the induction of TH elicited by either RO 20-1724 or PGE1. This delay is prevented by atropine. The elevation in cyclic AMP levels elicited by either RO 20-1724 or PGE1 is blocked for 1 h or 15 min. respectively, after treatment with carbachol. Cyclic AMP levels then begin to rise until they reach those levels observed in the presence of RO 20-1724 or PGE1 alone by 12 h or 1 h of treatment, respectively. Time course studies demonstrate that this transient inhibition of the elevation of cyclic AMP is associated with a 48-h delay in the induction of TH elicited by either RO 20-1724 or PGE1. In contrast, the induction elicited by 8-bromo cyclic AMP is unaffected by carbachol. A depolarizing concentration (56 mM) of KCl produces a 24-h delay in the induction of TH elicited by RO 20-1724, without affecting the concomitant elevation of cyclic AMP produced by the PDE inhibitor. Furthermore, 56 mM-KCl inhibits the induction of TH elicited by 8-bromo cyclic AMP. It thus appears that carbachol delays the induction of TH by transiently inhibiting the elevation of cyclic AMP, whereas potassium depolarization delays the induction of TH by inhibiting a process with a site of action that is distal to the elevation of cyclic AMP. 相似文献
10.
A pharmacological study was undertaken to determine whether the noradrenaline-stimulated breakdown of inositol phospholipids and the potentiation of isoprenaline-stimulated cyclic AMP by noradrenaline in rat cerebral cortex slices are mediated by the same alpha-receptor subtype. The rank order of potency of a range of alpha 1 and alpha 2 antagonists suggests that both responses may involve an alpha 1 receptor, but there were several differences between the pharmacological profiles for the two systems. Although in both cases, all selective alpha 1 antagonists were more potent than alpha 2 antagonists, the rank orders and the absolute potencies differed for the two responses. The inhibition of the inositol phosphate response was characterised by a high alpha 1/alpha 2 antagonist ratio, and in most cases, Hill slopes of inhibition were consistent with the involvement of a single receptor site. Inhibition of the cyclic AMP response had a much lower alpha 1/alpha 2 antagonist ratio and generally exhibited Hill slopes less than one. Evidence has been provided suggesting that adenosine is involved in the potentiation of cyclic AMP and that other, as yet unidentified, factors may also be involved. Even in the absence of an adenosine component, the results presented support the suggestion that the potentiation due to noradrenaline is mediated by a receptor whose identity does not easily fit with the currently accepted classification of alpha adrenoceptors. 相似文献
11.
Activation of Tyrosine Hydroxylase in PC12 Cells by the Cyclic GMP and Cyclic AMP Second Messenger Systems 总被引:2,自引:4,他引:2
Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by a variety of agents. Previous workers have found that cyclic AMP-dependent protein kinase and calcium-stimulated protein kinases activate tyrosine hydroxylase. We wanted to determine whether cyclic GMP might also be involved in the regulation of tyrosine hydroxylase activity. We found that treatment of rat PC12 cells with sodium nitroprusside (an activator of guanylate cyclase), 8-bromocyclic GMP, forskolin (an activator of adenylate cyclase), and 8-bromocyclic AMP all produced an increase in tyrosine hydroxylase activity measured in vitro or an increased conversion of [14C]tyrosine to labeled catecholamine in situ. Sodium nitroprusside also increased the relative synthesis of cyclic GMP in these cells. In the presence of MgATP, both cyclic GMP and cyclic AMP increased tyrosine hydroxylase activity in PC12 cell extracts. The heat-stable cyclic AMP-dependent protein kinase inhibitor failed to attenuate the activation produced in the presence of cyclic GMP. It eliminated the activation produced in the presence of cyclic AMP. Sodium nitroprusside also increased tyrosine hydroxylase activity in vitro in rat corpus striatal synaptosomes and bovine adrenal chromaffin cells. In all cases, the cyclic AMP-dependent activation of tyrosine hydroxylase was greater than that of the cyclic GMP-dependent second messenger system. These results indicate that both cyclic GMP and cyclic AMP and their cognate protein kinases activate tyrosine hydroxylase activity in PC12 cells. 相似文献
12.
Abstract: The adenosine A2a receptor inhibition of potassium (15 m M )-evoked GABA release from striatal nerve terminals has been examined. High extracellular calcium concentrations (4 m M ) reduced the effect of the A2a receptor agonist CGS-21680 (1 n M ). CGS-21680 inhibited GABA release in the presence of the L-type calcium channel blocker nifedipine, which itself inhibited evoked GABA release (by 16 ± 4%). ω-Conotoxin inhibited the evoked release by 45 ± 4% and prevented the action of CGS-21680. Forskolin and 8-bromo cyclic AMP both stimulated evoked GABA release at low concentrations, but at higher concentrations they abolished the inhibition by CGS-21680 without affecting the evoked release. The nonselective protein kinase inhibitor H-7 inhibited both the evoked release and the inhibition by CGS-21680, whereas the selective protein kinase A and G inhibitor HA-1004 had no effect on either evoked release or the action of CGS-21680. Pretreatment with pertussis toxin did not affect the A2a receptor-mediated inhibition. Therefore, the effect of A2a receptor stimulation was not mediated by protein kinases A or G but was inhibited by elevated cyclic AMP levels and mimicked by inhibitors of the N-type calcium channel and protein kinase C. 相似文献
13.
G. Casabona A. A. Genazzani M. Di Stefano M. A. Sortino F. Nicoletti 《Journal of neurochemistry》1992,59(3):1161-1163
Metabotropic glutamate receptors (mGluRs) have been recently described as a family of guanine nucleotide-binding regulatory protein-coupled receptors with multiple signal transduction pathways. At least one of these receptors appears to be negatively coupled to adenylyl cyclase when stably expressed in transfected cells. We have studied how activation of native mGluRs modulates cyclic AMP (cAMP) formation in brain slices prepared from rats at different ages. 1S,3R-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,1R-ACPD), a selective agonist of mGluRs, slightly increased basal cAMP formation but reduced forskolin-stimulated cAMP formation in adult hippocampal slices, in agreement with previous results. The action of 1S,3R-ACPD on basal cAMP formation was not reproduced by the ionotropic receptor agonists N-methyl-D-aspartate, kainate, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and was antagonised by L-2-amino-3-phosphonopropionate (L-AP-3). L-AP-3, however, did not prevent but rather mimicked the inhibitory action of 1S,3R-ACPD on forskolin-stimulated cAMP formation. In hippocampal slices from 1-, 8-, or 15-day-old rats, 1S,3R-ACPD increased basal cAMP formation but failed to reduce the action of forskolin. A similar development pattern of modulation was observed in hypothalamic slices with the difference that 1S,3R-ACPD did not stimulate basal cAMP formation in the hypothalamus of adult animals. These results suggest that inhibition of forskolin-stimulated cAMP formation by 1S,3R-ACPD is mediated by a specific mGluR subtype that is preferentially expressed in the adult. 相似文献
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15.
Laura Facci Stephen D. Skaper David L. Levin Silvio Varon 《Journal of neurochemistry》1987,48(2):566-573
Secondary microcultures of newborn rat cerebrum astroglial (AG) cells, maintained in a serum-free, chemically defined medium, were treated with various agents known to elevate intracellular cyclic AMP (cAMP) levels. Earlier studies had shown these drugs to induce a process-bearing (stellate) morphology in the AG cells, a response that was antagonized by the presence of gangliosides. One millimolar dibutyryl cyclic AMP (dBcAMP), 10 microM forskolin, 12 nM cholera toxin, and 30 microM isoproterenol all raised intracellular cAMP levels, from basal values of 3 pmol/10(6) cells to 30-30,000 pmol/10(6) cells, depending on the agent tested. dBcAMP caused the greatest elevation, and forskolin the least. The timing and/or the level of the AMP response did not precisely correlate with those of the stellation response. Values of ED50 with the four agents, as determined for the cAMP response, were always higher than stellation ED50 values in all treatments, and ED50 did not correlate with the maximal levels of cyclic AMP induced by the four agents. The capacity of ganglioside GM1 to block the stellation response to the four agents was not accompanied by a similar capacity to block the cAMP responses. Lysophosphatidylserine (lysoPS) had the capacity to induce AG cell stellation as well, without altering the basal level of cAMP. Both lysoPS and gangliosides, therefore, may act directly on the cellular machinery underlying the stellation response without involving changes in intracellular AMP. 相似文献
16.
The association of neurotensin to its receptor in differentiated neuroblastoma N1E115 cells led to a fast and transitory increase of the intracellular concentration in inositol triphosphate and inositol biphosphate, followed by a slower and more stable increase inositol monophosphate. The action of inositol 1,4,5-triphosphate on digitonin-permeabilized N1E115 cells resulted in a stimulation of cyclic GMP levels that mimicked that induced by neurotensin. Therefore, the cyclic GMP stimulation is probably a consequence of the initial inositol triphosphate formation triggered by neurotensin. Fluoroaluminate ions and pertussis toxin had the capacity to modulate positively and negatively, respectively, the formation of inositol triphosphate induced by neurotensin, indicating that GTP-binding proteins are involved in the regulation of inositol phosphate levels by neurotensin receptors. 相似文献
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18.
Victor C. Yu Steven Eiger Dah-Shuhn Duan Jelveh Lameh Wolfgang Sadée 《Journal of neurochemistry》1990,55(4):1390-1396
The human neuroblastoma clonal cell line SH-SY5Y expresses both mu- and delta-opioid receptors (ratio approximately 4.5:1). Differentiation with retinoic acid (RA) was previously shown to enhance the inhibition of adenylyl cyclase (AC) by mu-opioid agonists. We tested here the inhibition of cyclic AMP (cAMP) accumulation by morphine under a variety of conditions: after stimulation with prostaglandin E1 (PGE1), forskolin, and vasoactive intestinal peptide (VIP), both in the presence and in the absence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Morphine inhibition of the forskolin cAMP response (approximately 65%) was largely unaffected by the presence of IBMX. In contrast, deletion of IBMX enhanced morphine's inhibition of the PGE1 and VIP cAMP response from approximately 50 to approximately 80%. The use of highly mu- and delta-selective agents confirmed previous results that inhibition of cAMP accumulation by opioids is mostly mu, and not delta, receptor mediated in SH-SY5Y cells, regardless of the presence or absence of IBMX. Because of the large morphine inhibition and the high cAMP levels even in the absence of IBMX, PGE1-stimulated, RA-differentiated SH-SY5Y cells were subsequently used to study narcotic analgesic tolerance and dependence in vitro. Upon pretreatment with morphine over greater than or equal to 12 h, a fourfold shift of the PGE1-morphine dose-response curve was observed, whether or not IBMX was added. However, mu-opioid receptor number and affinity to the mu-selective [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin were largely unaffected, and Na(+)- and guanyl nucleotide-induced shifts of morphine-[3H]naloxone competition curves were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
19.
L. G. Abrahams M. A. Reutter K. E. McCarson V. S. Seybold 《Journal of neurochemistry》1999,73(1):50-58
Neurokinin1 (NK1) receptors are up-regulated in the spinal cord during peripheral inflammation, but the biochemical mediators regulating this change have not been resolved. The promoter region of the gene encoding the NK1 receptor contains a cyclic AMP (cAMP)-responsive element. Therefore, we used primary cultures of neonatal rat spinal cord to test whether increasing intracellular cAMP can increase expression of NK1 receptors. Treatment with dibutyryl-cAMP (dbcAMP) resulted in a time-dependent increase in 125I-Bolton-Hunter-substance P (BHSP) binding in the cultures; treatment with dibutyryl-cyclic GMP did not. Treatment with forskolin plus 3-isobutyl-1-methylxanthine mimicked the increase in binding, providing further evidence for the involvement of cAMP in this effect. Scatchard analyses indicated that the increase in BHSP binding was due to an increase in binding capacity. The cAMP-induced increase in BHSP binding was preceded by an increase in levels of mRNA for NK1 receptor and was attenuated by pretreatment with cycloheximide. These data indicate that the cAMP-induced increase in binding was due to increased synthesis of NK1 receptors. Comparison of substance P (SP)-induced production of inositol phosphates between cultures pretreated with dbcAMP and controls suggested that increased expression of NK1 receptors did not result in increased generation of second messenger by NK1 receptor activation. Together, these data indicate that a persistent increase in intracellular cAMP increases expression of NK1 receptors. Because NK1 receptor activation contributes to increased excitability of spinal neurons, the increased expression of NK1 receptors may be important in maintaining responsiveness of spinal neurons to SP in central mechanisms underlying hyperalgesia. 相似文献
20.
Zita Talaikytė Justas Barauskas Gediminas Niaura Irena Švedaitė Eugenijus Butkus Valdemaras Razumas Tommy Nylander 《Journal of biological physics》2004,30(1):83-96
Interactions of adenosine 3':5'-cyclicmonophosphate (cAMP) andN6,2'-O-dibutyryladenosine3':5'-cyclic monophosphate (dbcAMP) with alipid layer composed of monoolein-basedpreparation and dioleoylphosphatidylcholine (DOPC) wereinvestigated by small-angle X-raydiffraction (SAXD) and Raman spectroscopy.The reversed hexagonal (HII)MO/DOPC/H2O phase of 65:15:20 wt.%composition was selected as a referencesystem. SAXD revealed that entrapment (atthe expense of water) of 3 wt.% cAMP intothe reference system did not change thepolymorphic form and structural parametersof the phase. The same content of dbcAMPinduced the transition from the HIIphase to the reversed bicontinuous cubicphase of space group Ia3d. Thistransition is explained by the increase oflipid head-group area due to thepenetration of the acylated adenine groupof dbcAMP into the polar/apolar region oflipid layer. The conclusion is supported byRaman spectroscopy, showing thedisruption/weakening of hydrogen bonding inthe MO/DOPC-based matrix at the N1- andN3-sites of the dbcAMP adenine ring. Asdistinct from dbcAMP, cAMP remains mostlyin the water channels of the HIIphase, although the phosphate residue ofnucleotide interacts with the quaternaryammonium group of DOPC. Both nucleotidesincrease the population of gaucheisomers in the DOPC choline group. 相似文献