Arachidonic acid as a possible negative feedback inhibitor of nicotinic acetylcholine receptors on neurons

Vijayaraghavan, Sukumar; Huang, Bo; Blumenthal, Edward M.; Berg, Daniela

doi:10.1523/jneurosci.15-05-03679.1995

Cited by 93 publications

(74 citation statements)

References 62 publications

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“…In comparison to nAChRs, Bgt-nAChRs have faster kinetics of activation and desensitization, lower affinity for ACh and higher permeability to calcium 31,32 . Segregating nAChRs and Bgt-nAChRs to synaptic and perisynaptic (dendritic) surface regions, respectively, is likely to influence synaptic firing properties and establish distinct spatial and temporal patterns of calcium influx that may target different downstream signaling events in these local domains 33,34 .…”

Section: Discussionmentioning

confidence: 99%

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

et al. 1998

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ResultsUsing PCR, we constructed chimeric subunits in which the α7 cytoplasmic loop immediately after TM3 and before TM4 was replaced with the homologous region of the α3 or α5 sequence (Fig. 1a). The N-terminus up to TM2 regulates intersubunit assembly into receptor complexes, and α7 subunits do not coassemble with nAChR subunits, as demonstrated for endogenous subunits in CG neurons and for chimeric α7 subunits expressed in Xenopus laevis oocytes 4,5,12,13 . In particular, we have observed that coexpression of chimeric α7 subunits containing the α3 cytoplasmic loop together with wild-type α3 and β4 subunits in Xenopus oocytes results in the formation of two distinct receptor types that have the pharmacological properties of Bgt-nAChRs and nAChRs, respectively (data not shown). Thus, a difference in the distribution of chimeric α7 as compared to wild-type α7 on the infected CG neuron surface would result from the added α3 or α5 cytoplasmic loop. It cannot be explained by assembly with an endogenous nAChR subunit that can target to the synapse. Different types of neurotransmitter receptors coexist within single neurons and must be targeted to discrete synaptic regions for proper function. In chick ciliary ganglion neurons, nicotinic acetylcholine receptors (nAChRs) containing α3 and α5 subunits are concentrated in the postsynaptic membrane, whereas α-bungarotoxin receptors composed of α7 subunits are localized perisynaptically and excluded from the synapse. Using retroviral vector-mediated gene transfer in vivo, we show that the long cytoplasmic loop of α3 targets chimeric α7 subunits to the synapse and reduces endogenous nAChR surface levels, whereas the α5 loop does neither. These results show that a particular domain of one subunit targets specific receptor subtypes to the interneuronal synapse in vivo. Moreover, our findings suggest a difference in the mechanisms that govern assembly of interneuronal synapses as compared to the neuromuscular junction in vertebrates.1998 Nature America Inc.• http://neurosci.nature.com 1998 Nature America Inc.• http://neurosci.nature.com

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Section: Discussionmentioning

confidence: 99%

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

et al. 1998

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“…Last, but not least, the activation of nicotinic receptors on peripheral neurons has also been linked to altered phospholipid and fatty-acid metabolism (e.g., Vijayaraghavan et al, 1995;Marin et al, 1997;Stella and Piomelli, 2001;Tieman et al, 2001, and references therein). As several of these metabolites affect appetite and/or modulate nAChRs, the reciprocal interaction of nicotinic and lipid-signaling pathways may constitute an important "feedback" (pun intended) mechanism for regulating peripheral signals and circuits controlling food intake (e.g., Vijayaraghavan et al, 1995;Marin et al, 1997;Bray, 2000;Du and Role, 2001;Tieman et al, 2001).…”

Section: Does Nicotine Affect Appetite Via Interaction With Peripheramentioning

confidence: 99%

“…As several of these metabolites affect appetite and/or modulate nAChRs, the reciprocal interaction of nicotinic and lipid-signaling pathways may constitute an important "feedback" (pun intended) mechanism for regulating peripheral signals and circuits controlling food intake (e.g., Vijayaraghavan et al, 1995;Marin et al, 1997;Bray, 2000;Du and Role, 2001;Tieman et al, 2001).…”

Section: Does Nicotine Affect Appetite Via Interaction With Peripheramentioning

confidence: 99%

Nicotinic receptor‐mediated effects on appetite and food intake

Jo¹,

Talmage

Role³

2002

J. Neurobiol.

276

197

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ABSTRACT:It is well known, although not well understood, that smoking and eating just do not go together. Smoking is associated with decreased food intake and lower body weight. Nicotine, administered either by smoking or by smokeless routes, is considered the major appetite-suppressing component of tobacco. Perhaps the most renowned example of nicotine's influence on appetite and feeding behavior is the significant weight gain associated with smoking cessation. This article presents an overview of the literature at, or near, the interface of nicotinic receptors and appetite regulation. We first consider some of the possible sites of nicotine's action along the complex network of neural and non-neural regulators of feeding. We then present the hypothesis that the lateral hypothalamus is a particularly important locus of the anorectic effects of nicotine. Finally, we discuss the potential role of endogenous cholinergic systems in motivational feeding, focusing on cholinergic pathways in the lateral hypothalamus.

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“…Receptors coupled to PLA 2 via membrane G-proteins include cholinergic muscarinic M 1 and M 3 receptors, dopaminergic D 2 receptors, and serotonergic 5-HT 2 receptors (Axelrod, 1995;Bayon et al, 1997;Cooper et al, 1996;DeGeorge et al, 1991;Felder et al, 1990;Hayakawa et al, 2001;Vial and Piomelli, 1995). PLA 2 can also be activated when Ca 2+ enters cells by glutamate acting at N-methyl-d-aspartate (NMDA) receptors or by acetylcholine acting at nicotinic receptors (Brooks et al, 1989;Cooper et al, 1996;Vijayaraghavan et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Imaging Brain Phospholipase A2 Activation in Awake Rats in Response to the 5-HT2A/2C Agonist (±)2,5-Dimethoxy-4-Iodophenyl-2-Aminopropane (DOI)

Chang

Klaff

et al. 2002

Neuropsychopharmacol

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Incorporation coefficients k* of intravenously injected [ 3 H]arachidonic acid from blood into brain reflect the release from phospholipids of arachidonic acid by receptor-initiated activation of phospholipase A 2 (PLA 2 ). In unanesthetized adult rats, 2.5 mg/kg intraperitoneally (i.p.) ( 7 )2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), which is a 5-HT 2A/2C receptor agonist, has been reported to produce the behavioral changes of what is known as the 5-HT 2 syndrome, but only a few small regional decrements in brain glucose metabolism. In this study, 2.5 mg/kg i.p. DOI, when administered to unanesthetized rats, produced widespread and significant increases, of the order of 60%, in k* for arachidonate, particularly in neocortical brain regions reported to have high densities of 5-HT 2A receptors. The increases could be entirely blocked by chronic pretreatment with mianserin, a 5-HT 2 receptor antagonist. The results suggest that the 5-HT 2 syndrome involves widespread brain activation of PLA 2 via 5-HT 2A receptors, leading to the release of the second messenger, arachidonic acid. Chronic mianserin, a 5-HT 2 antagonist, prevents this activation.

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Arachidonic acid as a possible negative feedback inhibitor of nicotinic acetylcholine receptors on neurons

Abstract: for preparing the ciliary ganglion cell cultures, and Brtan Scott for preparing the Xenopcrs oocytes. The chicken a7 full-length construct used to generate RNA for expression i n oocytes was kindly provi ded by Dr. Ralf Schoepfer (Untversity of Heidelberg).

Cited by 93 publications

References 62 publications

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

Nicotinic receptor‐mediated effects on appetite and food intake

Imaging Brain Phospholipase A2 Activation in Awake Rats in Response to the 5-HT2A/2C Agonist (±)2,5-Dimethoxy-4-Iodophenyl-2-Aminopropane (DOI)

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