Developmental regulation of nicotinic acetylcholine receptor‐mediated [<sup>3</sup>H]norepinephrine release from rat cerebellum

O’Leary, Kathryn; Leslie, Frances M.

doi:10.1046/j.1471-4159.2003.01575.x

Cited by 38 publications

(23 citation statements)

References 65 publications

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“…In the rat cerebellum, another late-maturing structure, nicotine-evoked [ 3 H]NE release is significantly higher during the second to third postnatal week compared with the adult, similar to the situation observed in the present study for the mouse hippocampus (O'Leary and Leslie, 2003). The authors attributed the transient [ 3 H]NE release to key developmental events occurring during the period of observed peak release.…”

Section: Discussionsupporting

confidence: 88%

Characterization of Nicotinic Acetylcholine Receptors That Modulate Nicotine-Evoked [3H]Norepinephrine Release from Mouse Hippocampal Synaptosomes

Azam¹,

McIntosh²

2006

Molecular Pharmacology

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Nicotine's modulation of hippocampal noradrenergic neurotransmission may contribute to its mnemonic properties, but the nicotinic acetylcholine receptor (nAChR) subtypes that modulate terminal release of norepinephrine are unknown. In the present study, we used a number of subtype-selective ␣-conotoxins in combination with nicotinic receptor subunitdeficient mice to characterize nAChRs that modulate [ 3 H]norepinephrine release from synaptosomes. The results indicate that at least two populations of nAChRs contribute to this release: a novel ␣6(␣4)␤2␤3␤4 subtype and an ␣6(␣4)␤2␤3 subtype. These are distinct from subtypes that modulate synaptosomal norepinephrine release in the rat hippocampus in which an ␣6/␤2 and/or ␣6/␤4 ligand binding interface is not present. Whereas ␣-conotoxin MII fully inhibits nicotine-evoked 3 H]norepinephrine release by ␣-conotoxin BuIA, a toxin that kinetically distinguishes between ␤2-and ␤4-containing nAChRs, was partially reversible in mouse but irreversible in rat. This indicates that in contrast to rat, mouse nAChRs are made of both ␤4 and non-␤4-containing populations. Results from ␤2 and ␤4 null mutant mice confirmed this conclusion, indicating the presence of the ␤2 subunit in all nAChRs and the presence of the ␤4 subunit in a subpopulation of nAChRs. In addition, both ␣4 and ␤3 subunits are essential for the formation of functional nAChRs on mouse noradrenergic terminals. Cytisine, a ligand formerly believed to be ␤4-selective, was a highly effective agonist for ␣6␤2-containing nAChRs. The sum of these results suggests a possible novel nAChR subtype that modulates noradrenergic neurotransmission within the mouse hippocampus.

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Section: Discussionsupporting

confidence: 88%

Characterization of Nicotinic Acetylcholine Receptors That Modulate Nicotine-Evoked [3H]Norepinephrine Release from Mouse Hippocampal Synaptosomes

Azam¹,

McIntosh²

2006

Molecular Pharmacology

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“…Nicotine also acts centrally to stimulate dopamine release from nigrostriatal and mesocorticolimbic neurons and norepinephrine release from hippocampus, cerebellum, and locus coeruleus neurons (61)(62)(63). In agreement with these findings as well as our previous in vitro studies (1,7), here we documented acute nicotinic stimulation of catecholamine release as reflected by ϳ2.7-fold increments in plasma catecholamine levels (Fig.…”

Section: Stimulus-transcription Coupling In Vivo and The Role Of Nicosupporting

confidence: 92%

Catecholamine Secretory Vesicle Stimulus-Transcription Coupling in Vivo

Mahata¹,

Mahapatra²,

Mahata³

et al. 2003

Journal of Biological Chemistry

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Stimulation of the splanchnic (efferent, preganglionic sympathetic) nerves innervating the adrenal medulla and sympathetic postganglionic axons releases multiple neurotransmitters, including acetylcholine (acting on neuronal nicotinic cholinergic receptors), ATP, and chromogranin A, precursor of the catecholamine release inhibitory peptide "catestatin" (bovine chromogranin A 344 -364 ) (1).Chromogranin A, the major soluble protein in the core of amine and peptide hormone and neurotransmitter secretory vesicles (2, 3), plays both intracellular and extracellular roles. Within the catecholamine storage vesicle, chromogranin A plays a necessary role in vesiculogenesis and the ability to conduct regulated catecholamine secretion (4). Its extracellular roles derive from its biologically active proteolytic cleavage fragments (3): the catecholamine release-inhibitory fragment catestatin (bovine chromogranin A 344 -364 ) (1), the vasodilator vasostatin (bovine chromogranin A 1-76 ) (5), and the dysglycemic peptide pancreastatin (porcine chromogranin A 240 -288 ) (6).When secretory stimuli (such as acetylcholine interacting with nicotinic cholinergic receptors) trigger transmitter release from chromaffin cells or sympathetic axons, is the resynthesis of just released transmitters also initiated by the secretory stimulus? We have characterized this process (sometimes called "stimulus-secretion-synthesis coupling" or "stimulustranscription coupling") in chromaffin cells in vitro (7-9) and established transcriptional activation of chromogranin A by nicotinic cholinergic (physiologic pathway) stimulation. The process occurs at the level of transcript initiation (7), requires particular elements in cis in the proximal promoter (7), and has well defined signal transduction pathways in trans (8, 9). However, whether this nicotinic cholinergic stimulation of chromogranin A occurs in vivo is uncertain.We therefore set out to explore whether chromaffin cell stimulus-transcription coupling (specifically nicotinic cholinergic transcriptional stimulation of chromogranin A) occurs in vivo. To test this possibility, we employed a transgenic strain in which a mouse chromogranin A 4.8-kbp proximal promoter drives the expression of firefly luciferase, an extraordinarily sensitive reporter of gene expression (10 -12). In the in vivo experiments reported here, we used nicotine (mimicking the autonomic ganglionic transmitter acetylcholine) and reserpine (indirect stimulation by vesicular depletion) to evoke cate-

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“…In the developing brain, binding sites for nAChRs are detected during embryonic development in both human and animal fetuses (Cairns and Wonnacott, 1988;Hellstrom-Lindahl et al, 1998,Naeff et al, 1992,Tribollet et al, 2004Adams et al, 2002). In addition, there is evidence that the receptors are functional in prenatal and early postnatal rat pups (O'Leary andLeslie, 2003,Gallardo andLeslie, 1998). Therefore, gestational nicotine exposure could directly influence brain development.…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellum

2007

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Nicotine, the major psychoactive ingredient in tobacco interacting with nicotinic acetylcholine receptors (nAChR), is believed to have neuroprotective and neurotoxic effects on the developing brain. Neurotoxicity has been attributed to activation of homomeric α7 nAChRs, neuroprotection to heteromeric α4β2 nAChRs. Thus, developmental nicotine could have opposite effects in different brain regions, depending on nAChR subtype expression. Here, we determined if chronic neonatal nicotine exposure (CNN), during a period of brain growth corresponding to the third human trimester, differentially regulates nAChR expression, cell death, and morphological properties in hippocampus and cerebellum, two structures maturing postnatally. Rat pups were orally treated with 6 mg/kg/day nicotine from postnatal day (P)1 to P7. On P8, expression for α4, α7 and β2 mRNA was determined by in situ hybridization; nAChR binding sites in by receptor autoradiography, dying neurons by TUNEL and Fluoro-Jade staining and morphological properties by analysis of Cresyl-Violet stained sections. In control cerebellum, strong expression of α4, β2 mRNA and heteromeric nAChRs labeled with [ 125 I]-Epibatidine were found in granule cells, and α7 mRNA and homomeric nAChRs labeled with [ 125 I]-αBungarotoxin in the external germinal layer. In control hippocampus, low expression of α4 mRNA and heteromeric nAChRs and high expression of α7 mRNA and homomeric nAChRs were detected. CNN increased heteromeric nAChR binding in hippocampus but not cerebellum and significantly decreased neuronal soma size and increased packing density in hippocampal principal cells but not in cerebellum. CNN did not increase the number of dying cells in any area, but significantly fewer TUNEL-labeled cells were found in CA3 strata oriens and radiatum and cerebellar granule layer. Thus, the hippocampus seems to be more sensitive than the cerebellum to CNN which could result from different nAChR subtype expression and might explain long-lasting altered cognitive functions correlated with gestational nicotine exposure due to changes in hippocampal cell morphology.

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Developmental regulation of nicotinic acetylcholine receptor‐mediated [³H]norepinephrine release from rat cerebellum

Cited by 38 publications

References 65 publications

Characterization of Nicotinic Acetylcholine Receptors That Modulate Nicotine-Evoked [3H]Norepinephrine Release from Mouse Hippocampal Synaptosomes

Characterization of Nicotinic Acetylcholine Receptors That Modulate Nicotine-Evoked [3H]Norepinephrine Release from Mouse Hippocampal Synaptosomes

Catecholamine Secretory Vesicle Stimulus-Transcription Coupling in Vivo

Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellum

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Developmental regulation of nicotinic acetylcholine receptor‐mediated [3H]norepinephrine release from rat cerebellum

Cited by 38 publications

References 65 publications

Characterization of Nicotinic Acetylcholine Receptors That Modulate Nicotine-Evoked [3H]Norepinephrine Release from Mouse Hippocampal Synaptosomes

Characterization of Nicotinic Acetylcholine Receptors That Modulate Nicotine-Evoked [3H]Norepinephrine Release from Mouse Hippocampal Synaptosomes

Catecholamine Secretory Vesicle Stimulus-Transcription Coupling in Vivo

Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellum

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Developmental regulation of nicotinic acetylcholine receptor‐mediated [³H]norepinephrine release from rat cerebellum