Journal of Neurochemistry
Công bố khoa học tiêu biểu
* Dữ liệu chỉ mang tính chất tham khảo
Sắp xếp:
PACAP regulates immediate catecholamine release from adrenal chromaffin cells in an activity‐dependent manner through a protein kinase C‐dependent pathway Abstract Adrenal medullary chromaffin cells are a major peripheral output of the sympathetic nervous system. Catecholamine release from these cells is driven by synaptic excitation from the innervating splanchnic nerve. Acetylcholine has long been shown to be the primary transmitter at the splanchnic‐chromaffin synapse, acting through ionotropic nicotinic acetylcholine receptors to elicit action potential‐dependent secretion from the chromaffin cells. This cholinergic stimulation has been shown to desensitize under sustained stimulation, yet catecholamine release persists under this same condition. Recent evidence supports synaptic chromaffin cell stimulation through alternate transmitters. One candidate is pituitary adenylate cyclase activating peptide (PACAP), a peptide transmitter present in the adrenal medulla shown to have an excitatory effect on chromaffin cell secretion. In this study we utilize native neuronal stimulation of adrenal chromaffin cells in situ and amperometric catecholamine detection to demonstrate that PACAP specifically elicits catecholamine release under elevated splanchnic firing. Further data reveal that the immediate PACAP‐evoked stimulation involves a phospholipase C and protein kinase C‐dependant pathway to facilitate calcium influx through a Ni2+ and mibefradil‐sensitive calcium conductance that results in catecholamine release. These data demonstrate that PACAP acts as a primary secretagogue at the sympatho‐adrenal synapse under the stress response.
Journal of Neurochemistry - Tập 110 Số 4 - Trang 1214-1225 - 2009
Substance P Protects Against Desensitization of the Nicotinic Response in Isolated Adrenal Chromaffin Cells Abstract: Substance P, a peptide endogenous to the splanchnic nerve, is known to inhibit the acetylcholineand nicotine‐induced release of catecholamines from isolated adrenal chromaffin cells. In the present study the effect of substance P on desensitization of catecholamine release from these cells was examined. Substance P (10−5 M ) completely protected against desensitization of catecholamine release produced by acetylcholine at 37°C or 23°C and by nicotine at 23°C; substance P also afforded appreciable protection against nicotine‐induced desensitization at 37°C. The peptide had no effect on K+ ‐induced desensitization of catecholamine release. Like substance P, d ‐tubocurarine also prevented nicotinic desensitization. Substance P prevented both of two components of nicotinic desensitization, i.e. the Ca2+ ‐dependent component and the Ca2+ ‐independent, depletion‐independent component of desensitization. Substance P had little effect on subsequent catecholamine uptake, indicating that substance P's protection against desensitization is a result of facilitation of catecholamine release rather than inhibition of catecholamine reuptake. Nicotine‐induced catecholamine release and nicotinic desensitization of catecholamine release were Na+ ‐independent, although substance P's inhibition of nicotine‐induced catecholamine release was reduced by extracellular Na+ . These in vitro studies suggest a similar role for substance P in vivo: substance P's protection against nicotinic desensitization may ensure a maintained output of adrenal catecholamines during stress, when the splanchnic nerve releases large amounts of acetylcholine.
Journal of Neurochemistry - Tập 42 Số 3 - Trang 618-627 - 1984
Distinct Muscarinic Receptor Subtypes Differentially Modulate Acetylcholine Release from Corticocerebral Synaptosomes Abstract The effect of McN‐A‐343 and oxotremorine on acetylcholine (ACh) release and choline (Ch) transport was studied in corticocerebral synaptosomes of the guinea pig. The synaptosomes were preloaded with [3 H]Ch after treatment with the irreversible cholinesterase inhibitor, diisopropyl fluorophosphate, and then tested for their ability to release isotope‐labeled ACh and Ch in the presence and absence of these agents. The kinetics of release were determined at the resting state (basal release) and in the presence of 50 mM K+ . Under either condition, McN‐A‐343 enhanced the release of isotope‐labeled ACh, whereas oxotremorine inhibited the K+ ‐evoked release but had no effect on the basal release. The enhancing effect of McN‐A‐343 on basal ACh release was fully blocked by the selective M1 muscarinic antagonist, pirenzepine (100 nM ). In contrast to its enhancing effect on ACh release, McN‐A‐343 potently inhibited Ch efflux as well as Ch influx. These effects were not blocked by atropine, a nonselective muscarinic antagonist. Oxotremorine had no effect on Ch transport. Binding studies showed that McN‐A‐343 was 3.6‐fold more potent in displacing radiolabeled quinuclidinyl benzilate from cerebral cortex muscarinic receptors (mostly M1 subtype) than from cerebellar receptors (mostly M2 subtype), whereas oxotremorine was 2.6‐fold more potent in the cerebellum. The displacements of radio‐labeled pirenzepine and m‐dioxolane confirmed the M1 subtype preference of McN‐A‐343 and the M2 subtype preference of oxotremorine. These observations suggest that (a) activation of one subpopulation of muscarinic receptors by McN‐A‐343 enhances ACh release, whereas activation of another subpopulation by oxotremorine decreases this process (these subpopulations may correspond to the M1 and M2 subtypes, respectively), (b) the effect of the stimulatory receptors is pronounced at the resting state and that of the inhibitory receptors during depolarization, and (c) activation of the stimulatory receptors may be inversely related to the activity of the Ch transporter.
Journal of Neurochemistry - Tập 55 Số 2 - Trang 665-672 - 1990
Drug Effects on the Release of Endogenous Acetylcholine In Vivo: Measurement by Intracerebral Dialysis and Gas Chromatography–Mass Spectrometry Abstract: Intracerebral microdialysis was combined with a sensitive and specific gas chromatographic–mass spectrometric assay to measure the release of endogenous acetylcholine in the rat striatum in vivo. In rats anesthetized with urethane (1.2 g/kg i.p.), the levels of striatal acetylcholine dialyzed into a Ringer's perfusate were: (a) reliably measurable only in the presence of physostigmine; (b) stable at between 3 and 8 h of perfusion (30–75 pmol/20 min in the presence of 75 μM physostigmine); (c) reduced by calcium‐free Ringer's solution, tetrodotoxin (0.1 μM ), and vesamicol (1.0 μM ); and (d) increased by elevated potassium (100 mM ), atropine (3–300 μM ), and haloperidol (0.75 mg/kg i.p.). In conscious unrestrained rats, the spontaneous release of striatal acetylcholine was not altered significantly following the administration of urethane. The changes in acetylcholine release observed in this study are consistent with the known actions of some drugs or ionic conditions on striatal cholinergic neurotransmission and are evident under the condition of urethane anesthesia. The present results demonstrate the sensitivity and suitability of this method for monitoring endogenous striatal acetylcholine release in vivo.
Journal of Neurochemistry - Tập 54 Số 6 - Trang 2016-2023 - 1990
Extracellular‐Regulated Kinases and Phosphatidylinositol 3‐Kinase Are Involved in Brain‐Derived Neurotrophic Factor‐Mediated Survival and neuritogenesis of the Neuroblastoma Cell Line SH‐SY5Y Abstract : Retinoic acid (RA) induces the differentiation of many cell lines, including those derived from neuroblastoma. RA treatment of SH‐SY5Y cells induces the appearance of functional Trk B and Trk C receptors. Acute stimulation of RA‐predifferentiated SH‐SY5Y cells with brain‐derived neurotrophic factor (BDNF), neurotrophin 3 (NT‐3), or neurotrophin 4/5 (NT‐4/5), but not nerve growth factor (NGF), induces Trk autophosphorylation, followed by phosphorylation of Akt and the extracellular signal‐regulated kinases (ERKs) 1 and 2. In addition, BDNF, NT‐3, or NT‐4/5, but not NGF, promotes cell survival and neurite outgrowth in serum‐free medium. The mitogen‐activated protein kinase and ERK kinase (MEK) inhibitor PD98059 blocks BDNF‐induced neurite outgrowth and growth‐associated protein‐43 expression but has no effects on cell survival. On the other hand, the phosphatidylinositol 3‐kinase inhibitor LY249002 reverses the survival response elicited by BDNF, leading to a cell death with morphological features of apoptosis.
Journal of Neurochemistry - Tập 73 Số 4 - Trang 1409-1421 - 1999
PINEAL DOPA DECARBOXYLASE AND MONOAMINE OXIDASE ACTIVITIES AS RELATED TO THE MONOAMINE STORES
Journal of Neurochemistry - Tập 13 Số 7 - Trang 597-605 - 1966
STORAGE, SYNTHESIS, AND METABOLISM OF MONOAMINES IN THE DEVELOPING BRAIN
Journal of Neurochemistry - Tập 9 Số 1 - Trang 53-58 - 1962
Stromal cell‐derived factor‐1α directly modulates voltage‐dependent currents of the action potential in mammalian neuronal cells Abstract Stromal cell‐derived factor‐1α (SDF‐1α) is a chemokine whose receptor, CXCR4, is distributed in specific brain areas including hypothalamus. SDF‐1α has recently been found to play important roles in neurons, although direct modulation of voltage‐gated ionic channels has never been shown. In order to clarify this issue, we performed patch‐clamp experiments in fetal mouse hypothalamic neurons in culture. SDF‐1α (10 nm ) decreased the peak and rising slope of the action potentials and spike discharge frequency in 22% of hypothalamic neurons tested. This effect was blocked by the CXCR4 antagonist AMD 3100 (1 µm ) but not by the metabotropic glutamate receptor antagonist MCPG (500 µm ), indicating a direct action of SDF‐1α on its cognate receptor. This effect involved a depression of both inward and outward voltage‐dependent currents of the action potential. We confirmed these effects in the human neuroblastoma cell line SH‐SY5Y, which endogenously expresses CXCR4. Voltage‐clamp experiments revealed that SDF‐1α induced a 20% decrease in the peak of the tetrodotoxin‐sensitive sodium current and tetraethylammonium‐sensitive delayed rectifier potassium current, respectively. Both effects were concentration dependent, and blocked by AMD 3100 (200 nm ). This dual effect was reduced or blocked by 0.4 mm GTPγS G‐protein pre‐activation or by pre‐treatment with the G‐protein inhibitor pertussis toxin (200 ng/mL), suggesting that it is mediated via activation of a Gi/o protein. This study extends the functions of SDF‐1α to a direct modulation of voltage‐dependent membrane currents of neuronal cells.
Journal of Neurochemistry - Tập 93 Số 4 - Trang 963-973 - 2005
Glial and Neuronal Cells Express Functional Chemokine Receptor CXCR4 and Its Natural Ligand Stromal Cell‐Derived Factor 1 Abstract : Chemokines are a family of proteins that chemoattract and activate cells by interacting with specific receptors on the surface of their targets. The chemokine stromal cell‐derived factor 1, (SDF1), binds to the seventransmembrane G protein‐coupled CXCR4 receptor and acts to modulate cell migration, differentiation, and proliferation. CXCR4 and SDF1 are reported to be expressed in various tissues including brain. Here we show that SDF1 and CXCR4 are expressed in cultured cortical type I rat astrocytes, cortical neurons, and cerebellar granule cells. In cortical astrocytes, prolonged treatment with lipopolysaccharide induced an increase of SDF1 expression and a down‐regulation of CXCR4, whereas treatment with phorbol esters did not affect SDF1 expression and down‐modulated CXCR4 receptor expression. We also demonstrated the ability of human SDF1α (hSDF1α) to increase the intracellular calcium level in cultured astrocytes and cortical neurons, whereas in the same conditions, cerebellar granule cells did not modify their intracellular calcium concentration. Furthermore, in cortical astrocytes, the simultaneous treatment of hSDF1α with the HIV‐1 capside glycoprotein gp120 inhibits the cyclic AMP formation induced by forskolin treatment.
Journal of Neurochemistry - Tập 73 Số 6 - Trang 2348-2357 - 1999
Stromal cell‐derived factor‐1α induces astrocyte proliferation through the activation of extracellular signal‐regulated kinases 1/2 pathway Stromal cell‐derived factor‐1 (SDF‐1), the ligand of the CXCR4 receptor, is a chemokine involved in chemotaxis and brain development that also acts as co‐receptor for HIV‐1 infection. We previously demonstrated that CXCR4 and SDF‐1α are expressed in cultured type‐I cortical rat astrocytes, cortical neurones and cerebellar granule cells. Here, we investigated the possible functions of CXCR4 expressed in rat type‐I cortical astrocytes and demonstrated that SDF‐1α stimulated the proliferation of these cells in vitro . The proliferative activity induced by SDF‐1α in astrocytes was reduced by PD98059, indicating the involvement of extracellular signal‐regulated kinases (ERK1/2) in the astrocyte proliferation induced by CXCR4 stimulation. This observation was further confirmed showing that SDF‐1α treatment selectively activated ERK1/2, but not p38 or stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK). Moreover, both astrocyte proliferation and ERK1/2 phosphorylation, induced by SDF‐1α, were inhibited by pertussis toxin (PTX) and wortmannin treatment indicating the involvement of a PTX sensitive G‐protein and of phosphatidyl inositol‐3 kinase in the signalling of SDF‐1α. In addition, Pyk2 activation represent an upstream components for the CXCR4 signalling to ERK1/2 in astrocytes. To our knowledge, this is the first report demonstrating a proliferative effect for SDF‐1α in primary cultures of rat type‐I astrocytes, and showing that the activation of ERK1/2 is responsible for this effect. These data suggest that CXCR4/SDF‐1 should play an important role in physiological and pathological glial proliferation, such as brain development, reactive gliosis and brain tumour formation.
Journal of Neurochemistry - Tập 77 Số 5 - Trang 1226-1236 - 2001
Tổng số: 734
- 1
- 2
- 3
- 4
- 5
- 6
- 10