Influence of acetylcholine levels on the binding of a SPECT nicotinic acetylcholine receptor ligand [123I]5‐I‐A‐85380
Abstract
Although in vitro theory indicates that ligand binding is sensitive to competition with neurotransmitters, only some imaging ligands have shown such competition in vivo. The purpose of this study was to determine whether increases in acetylcholine (ACh) levels induced by an acetylcholinesterase inhibitor, physostigmine, inhibit in vivo binding of [123 I]5‐iodo‐3‐(2(S)‐2‐azetidinyl‐methoxy) pyridine (5‐I‐A‐85380), a single photon emission computed tomography ligand for the high‐affinity type nicotinic ACh receptor (nAChR). Baboons were used for seven studies with a bolus plus constant infusion equilibrium paradigm. After achieving equilibrium at 5 h, physostigmine (0.02 (n = 1), 0.067 (n = 3), and 0.2 (n = 3) mg/kg) was administered intravenously and data were acquired for up to 8 h. To confirm equilibrium conditions, [123 I]5‐I‐A‐85380 plasma levels were measured in four studies, including all studies with 0.2 mg/kg physostigmine. Prior to physostigmine administration, thalamic activities were stable, with changes of 1.1%/h or less, except in one study with a gradual increase of 4.2%/h. Thalamic activities were decreased by 15% in one study with 0.067 mg/kg and 14–17% in all studies with 0.2 mg/kg physostigmine administration (P = 0.009). In these studies with 0.2 mg/kg physostigmine administration, [123 I]5‐I‐A‐85380 plasma levels showed a transient or a sustained increase after physostigmine administration that would have increased thalamic activities. These results suggest that elevated ACh levels induced by physostigmine can effectively compete in vivo with [123 I]5‐I‐A‐85380 binding at nAChRs. However, decreased thalamic activities could have been caused by other mechanisms, including internalization of the receptor with an associated decreased affinity for radioligand. Synapse 48:116–122, 2003. © 2003 Wiley‐Liss, Inc.
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In nonhuman primates, elevated ACh levels induced by a high dose of intravenous physostigmine can compete effectively in vivo with [123I]5-IA binding at β2*-nAChRs.
“It has been shown previously in nonhuman primates that elevated ACh levels induced by a high dose of intravenous physostigmine, an acetylcholinesterase inhibitor, can compete effectively in vivo with [123I]5-IA binding at β2*-nAChRs (27).”
From Persistent β <sub>2</sub> *-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder (2012) · cites this paper as [27]
When β2*-nAChR availability is measured in the absence of bound endogenous ACh, there is no evidence of a change in receptor number.
“These results, together with the non-human primate study (27), suggest that when β2*-nAChR availability is measured in the absence of bound endogenous ACh, there is no evidence of a change in receptor number.”
From Persistent β <sub>2</sub> *-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder (2012) · cites this paper as [27]
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- Authors
- Fujita, M., Al‐Tikriti, M. S., Tamagnan, G., Zoghbi, S. S., Bozkurt, A., Baldwin, R. M., & Innis, R. B.
- Affiliations
- Yale University (US)
- Corresponding author
- Fujita, Masahiro
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 2003-03-10
- Volume
- 48
- Issue
- 3
- Pages
- 116-122
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- OpenAlex
- W2142237115
- Cited by
- 24
- References
- 45
- Citations by year
- 2024: 1 · 2020: 1 · 2018: 1 · 2016: 1 · 2014: 2 · 2013: 2 · 2012: 4
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Synapse (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (P50-DA84733)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- acetylcholine, nicotinic acetylcholine receptors, physostigmine, acetylcholinesterase inhibition, thalamic activity, baboons, receptor internalization
- MeSH terms
- Acetylcholine, Animals, Azetidines, Binding, Competitive, Brain, Cholinesterase Inhibitors, Female, Image Processing, Computer-Assisted, Iodine Radioisotopes, Ligands, Magnetic Resonance Imaging, Ovariectomy, Papio, Physostigmine, Radiography, Receptors, Nicotinic, Tomography, Emission-Computed, Single-Photon
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