Desensitization of Nicotine‐Stimulated [3H]Dopamine Release from Mouse Striatal Synaptosomes

Grady, Sharon R.; Marks, Michael J.; Collins, Allan C.

doi:10.1046/j.1471-4159.1994.62041390.x

Cited by 126Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchReceptor Mechanisms and Signaling

Desensitization of Nicotine‐Stimulated [3H]Dopamine Release from Mouse Striatal Synaptosomes

Grady, Sharon R., Marks, Michael J., Collins, Allan C.·1994·Journal of Neurochemistry

DOI 10.1046/j.1471-4159.1994.62041390.x

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Abstract

Potential desensitization of brain nicotinic receptors was studied using a [3H]dopamine release assay. Nicotine-stimulated [3H]dopamine release from mouse striatal synaptosomes was concentration-dependent with an EC50 of 0.33 +/- 0.13 microM and a Hill coefficient of 1.44 +/- 0.18. Desensitization by activating concentrations of nicotine had a similar EC50 and a half-time of 35 s. Concentrations of nicotine that evoked little release also induced a concentration-dependent desensitization (EC50 = 6.9 +/- 3.6 nM, t1/2 = 1.6-2.0 min, nH = 1.02 +/- 0.01). Both types of desensitization produced a maximum 75% decrease in [3H]dopamine release. Recovery from desensitization after exposure to low or activating concentrations of nicotine was time-dependent with half-times of 6.1 min and 12.4 min, respectively. Constants determined for binding of [3H]nicotine to striatal membrane at 22 degrees C included a KD of 3.7 +/- 0.5 nM, Bmax of 67.5 +/- 2.2 fmol/mg, and Hill coefficient of 1.07 +/- 0.06. Association of nicotine with membrane binding sites was biphasic with half-times of 9 s and 1.8 min. The fast rate process contributed 37% of the total reaction. Dissociation was a uniphasic process with a half-time of 1.6 min. Comparison of constants determined by the release and binding assays indicated that the [3H]-nicotine binding site could be the presynaptic receptor involved in [3H]dopamine release in mouse striatal synaptosomes.

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Lower doses of nicotine, consistent with those in the blood of human smokers, result in desensitization rather than activation of nAChRs as measured by nicotine-dependent dopamine release in striatal synaptosomes.
“Studies in striatal synaptosomes, however, show that lower doses of nicotine, consistent with those in the blood of human smokers, result in desensitization rather than activation of nAChRs as measured by nicotine-dependent dopamine release (Grady et al., 1992; Grady et al., 1994; Rowell and Duggan, 1998; Rowell and Hillebrand, 1994).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Grady et al., 1994
Nicotine strongly desensitizes nicotinic receptors.
“Nicotine potently desensitizes nAChRs (Sharp and Beyer, 1986;Hulihan-Giblin et al., 1990;Grady et al., 1994;Marks et al., 1994;Lester and Dani, 1995;Pidoplichko et al., 1997; for reviews, see Meyer et al., 2001;Picciotto et al., 2008;Buccafusco et al., 2009);”
From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Grady et al., 1994
In isolated preparations, nicotine can desensitize these receptors at concentrations up to 45-fold lower than those needed to activate them.
“and up to 45 times more potent in vitro (Grady et al., 1994;Marks et al., 1994).”
From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Grady et al., 1994
Chronic nicotine exposure induces up-regulation of nAChRs and profound desensitization of these receptors in vitro.
“Chronic nicotine exposure induces up-regulation of nAChRs, but also profound desensitization of these receptors in vitro (Fenster et al., 1997; Grady et al., 1994).”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Grady et al., 1994

PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,199 · see citing works
Enzyme Kinetics Behavior and analysis of rapid equilibrium and steady state enzyme systems
Gutfreund, H. (1975) · FEBS Letters · doi:10.1016/0014-5793(75)80457-1 · Cited by 1,508 · see citing works
A study of the ‘desensitization’ produced by acetylcholine at the motor end‐plate
Katz, B., & Thesleff, S. (1957) · The Journal of Physiology · doi:10.1113/jphysiol.1957.sp005838 · Cited by 1,463 · see citing works
A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment.
Flores, C. M., Rogers, S. W., Pabreza, L. A., Wolfe, B. B., & Kellar, K. J. (1992) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08832-7 · Cited by 880 · see citing works
Multiple calcium-dependent processes related to secretion in bovine chromaffin cells
Neher, E., & Zucker, R. S. (1993) · Neuron · doi:10.1016/0896-6273(93)90238-m · Cited by 526 · see citing works
Characterization of Nicotinic Receptor‐Mediated [<sup>3</sup>H]Dopamine Release from Synaptosomes Prepared from Mouse Striatum
Grady, S., Marks, M. J., Wonnacott, S., & Collins, A. C. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08322.x · Cited by 350 · see citing works
Self-citation
Rapid Preparation of Synaptosomes from Mammalian Brain Using Nontoxic Isoosmotic Gradient Material (Percoll)
Nagy, A. K., & Delgado‐Escueta, A. V. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb12851.x · Cited by 343 · see citing works
Stereospecific Nicotine Receptors on Rat Brain Membranes
Romano, C., & D, A. G. M. (1980) · Science · doi:10.1126/science.7433991 · Cited by 318 · see citing works
In Vivo Regulation of [3H]Acetylcholine Recognition Sites in Brain by Nicotinic Cholinergic Drugs
Schwartz, R. D., & Kellar, K. J. (1985) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1985.tb04005.x · Cited by 282 · see citing works
Nicotinic binding sites in rat and mouse brain: comparison of acetylcholine, nicotine, and alpha-bungarotoxin.
Marks, M. J., Stitzel, J. A., Romm, E., Wehner, J. M., & Collins, A. C. (1986) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10395-7 · Cited by 267 · see citing works
Self-citation
Cell Surface Receptors: A Short Course on Theory and Methods
Limbird, L. E. (1986) · Springer eBooks · doi:10.1007/978-1-4757-1882-9 · Cited by 251 · see citing works
Neurotoxins Distinguish Between Different Neuronal Nicotinic Acetylcholine Receptor Subunit Combinations
Luetje, C. W., Wada, K., Rogers, S. W., Abramson, S. N., Tsuji, K., Heinemann, S., & Patrick, J. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb04180.x · Cited by 228 · see citing works
Stereoselective Nicotine‐Induced Release of Dopamine from Striatal Synaptosomes: Concentration Dependence and Repetitive Stimulation
RAPIER, C. M., Lunt, G. G., & Wonnacott, S. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb10582.x · Cited by 206 · see citing works
Desensitization of the nicotinic acetylcholine receptor: Molecular mechanisms and effect of modulators
Ochoa, E. L. M., Chattopadhyay, A., & McNamee, M. G. (1989) · Cellular and Molecular Neurobiology · doi:10.1007/bf00713026 · Cited by 206 · see citing works
Structural and Pharmacological Characterization of the Major Brain Nicotinic Acetylcholine Receptor Subtype Stably Expressed in Mouse Fibroblasts
Whiting, P. J., Schoepfer, R., Lindström, J., & Priestley, T. (1991) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)15355-8 · Cited by 200 · see citing works
The expression of nicotinic acetylcholine receptors by PC12 cells treated with NGF
Rogers, S., Mandelzys, A., Deneris, E. S., Cooper, E. A., & Heinemann, S. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-12-04611.1992 · Cited by 162 · see citing works
Nicotine receptors in the mammalian brain
Luetje, C. W., Patrick, J., & Séguéla, P. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.10.2197155 · Cited by 147 · see citing works
Nicotinic receptor function determined by stimulation of rubidium efflux from mouse brain synaptosomes.
Marks, M. J., Farnham, D. A., Grady, S. R., & Collins, A. C. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10175-4 · Cited by 112 · see citing works
Self-citation
Heterogeneity and Regulation of Nicotinic Acetylcholine Receptors
Lukas, R. J., & Bencherif, M. (1992) · International review of neurobiology · doi:10.1016/s0074-7742(08)60097-5 · Cited by 95 · see citing works
Two distinct kinetic phases of desensitization of acetylcholine receptors of clonal rat PC12 cells.
Boyd, N. D. (1987) · The Journal of Physiology · doi:10.1113/jphysiol.1987.sp016646 · Cited by 95 · see citing works
Desensitization to Nicotinic Cholinergic Agonists and K+, Agents That Stimulate Catecholamine Secretion, in Isolated Adrenal Chromaffin Cells
Boksa, P., & Livett, B. G. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb02726.x · Cited by 92 · see citing works
Neuronal bungarotoxin blocks the nicotinic stimulation of endogenous dopamine release from rat striatum
Schulz, D. W., & Zigmond, R. E. (1989) · Neuroscience Letters · doi:10.1016/0304-3940(89)90420-5 · Cited by 81 · see citing works
Effects of Chronic Nicotinic Ligand Exposure on Functional Activity of Nicotinic Acetylcholine Receptors Expressed by Cells of the PC12 Rat Pheochromocytoma or the TE671/RD Human Clonal Line
Lukas, R. J. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb11403.x · Cited by 79 · see citing works
Pharmacological distinctions between functional nicotinic acetylcholine receptors on the PC12 rat pheochromocytoma and the TE671 human medulloblastoma.
Lukas, R. J. (1989) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20697-8 · Cited by 69 · see citing works
Substance P Protects Against Desensitization of the Nicotinic Response in Isolated Adrenal Chromaffin Cells
Boksa, P., & Livett, B. G. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb02727.x · Cited by 65 · see citing works
Kinetics and mechanism of L-[3H]nicotine binding to putative high affinity receptor sites in rat brain.
Lippiello, P. M., Sears, S. B., & Fernandes, K. G. (1987) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10448-3 · Cited by 65 · see citing works
Neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes: role of the ? subunit in agonist sensitivity and desensitization
Gross, A., Ballivet, M., Rungger, D., et al. (1991) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00370805 · Cited by 62 · see citing works
A desensitized form of neuronal acetylcholine receptor detected by 3H- nicotine binding on bovine adrenal chromaffin cells [published erratum appears in J Neurosci 1988 Dec;8(12):preceding 4415]
Higgins, L., & Berg, D. K. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-04-01436.1988 · Cited by 53 · see citing works
Immunological identification of a nicotinic acetylcholine receptor on bovine chromaffin cells
Higgins, L., & Berg, D. K. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-06-01792.1987 · Cited by 48 · see citing works
Effects of Substance P on Nicotinic Acetylcholine Receptor Function in PC 12 Cells
Simasko, S. M., Durkin, J. A., & Weiland, G. A. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb03423.x · Cited by 40 · see citing works
Desensitization of the nicotinic secretory response of adrenal chromaffin cells
Marley, P. D. (1988) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(88)90177-0 · Cited by 37 · see citing works
Agonist-induced regulation of the neuronal nicotinic acetylcholine receptor of PC12 cells.
Robinson, D. E., & McGee, R. (1985) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)12382-1 · Cited by 35 · see citing works
Identification of cultured cells expressing ligand-gated cationic channels
Rogers, S. W., Gahring, L. C., Papke, R. L., & Heinemann, S. (1991) · Protein Expression and Purification · doi:10.1016/1046-5928(91)90058-q · Cited by 18 · see citing works

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Quick, M. W., & Lester, R. A. J. (2002) · Journal of Neurobiology · doi:10.1002/neu.10109 · Cited by 456 · see citing works
It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood
PICCIOTTO, M., ADDY, N., MINEUR, Y., & BRUNZELL, D. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.12.005 · Cited by 451 · see citing works
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Frazier, C. J., Rollins, Y. D., Breese, C. R., Leonard, S., Freedman, R., & Dunwiddie, T. V. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-04-01187.1998 · Cited by 374 · see citing works
Reward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366 · see citing works
“The dense striatal acetylcholine esterase rapidly hydrolyzes the released ACh, preventing the appearance of long-lasting ACh signals that would strongly desensitize the high-affinity subtypes of nAChRs (Dani et al. 2000, Grady et al. 1994, Wooltorton et al. 2003).”
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Govind, A. P., Vezina, P., & Green, W. N. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.06.011 · Cited by 338 · see citing works
The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum
Grady, S. R., Salminen, O., Laverty, D. C., Whiteaker, P., McIntosh, J. M., Collins, A. C., & Marks, M. J. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.032 · Cited by 252 · see citing works
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Fenster, C. P., Whitworth, T. L., Sheffield, E. B., Quick, M. W., & Lester, R. A. J. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-12-04804.1999 · Cited by 204 · see citing works
Dose‐related neuroprotective effects of chronic nicotine in 6‐hydroxydopamine treated rats, and loss of neuroprotection in α4 nicotinic receptor subunit knockout mice
Ryan, R. E., Ross, S. A., Drago, J., & Loiacono, R. E. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703989 · Cited by 188 · see citing works
Nicotinic receptors in human brain: topography and pathology
Court, J. A., Martin-Ruiz, C., Graham, A., & Perry, E. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00110-1 · Cited by 180 · see citing works
Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states
Picciotto, M. R., Lewis, A. S., van Schalkwyk, G. I., & Mineur, Y. S. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.12.028 · Cited by 157 · see citing works
Sazetidine-A, A Novel Ligand That Desensitizes α4β2 Nicotinic Acetylcholine Receptors without Activating Them
Xiao, Y., Fan, H., Musachio, J. L., Wei, Z.-L., Chellappan, S. K., Kozikowski, A. P., & Kellar, K. J. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027318 · Cited by 141 · see citing works
Dopamine and nicotinic receptor binding and the levels of dopamine and homovanillic acid in human brain related to tobacco use
Court, J. A., Lloyd, S., Thomas, N., Piggott, M. A., Marshall, E. F., Morris, C. M., Lamb, H., Perry, R. H., Johnson, M., & Perry, E. K. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00088-8 · Cited by 135 · see citing works
(S)-(−)-cotinine, the major brain metabolite of nicotine, stimulates nicotinic receptors to evoke [3H]dopamine release from rat striatal slices in a calcium-dependent manner
Dwoskin, L. P., Teng, L., Buxton, S. T., & Crooks, P. A. (1999) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38040-1 · Cited by 120 · see citing works
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Hussmann, G. P., Turner, J. R., Lomazzo, E., Venkatesh, R., Cousins, V., Xiao, Y., Yasuda, R. P., Wolfe, B. B., Perry, D. C., Rezvani, A. H., et al. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.198085 · Cited by 34 · see citing works

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Tammimäki, A., Chistyakov, V., Patkina, N. A., Skippari, J., Ahtee, L., Zvartau, E. E., & Männistö, P. T. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.06.081 · Cited by 16 · see citing works
Group desensitization of dissimilar anxieties
Deffenbacher, J. L. (1976) · Community Mental Health Journal · doi:10.1007/bf01419753 · Cited by 1 · see citing works
Research progress on desensitization of hypersensitivity reaction to iodinated contrast media
Fan, M., Zheng, X., & Zhu, S. (2023) · Journal of Zhejiang University (Medical Sciences) · doi:10.3724/zdxbyxb-2023-0220
Exposure to nicotine during a defined period in neonatal life induces permanent changes in brain nicotinic receptors and in behaviour of adult mice.
Eriksson, P., Ankarberg, E., & Fredriksson, A. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02231-3 · Cited by 124 · see citing works
Nicotine levels after IV nicotine and cigarette smoking in men.
Mello, N. K., Peltier, M. R., & Duncanson, H. (2013) · Experimental and Clinical Psychopharmacology · doi:10.1037/a0031799 · Cited by 16 · see citing works

Authors: Grady, S. R., Marks, M. J., & Collins, A. C.
Affiliations: University of Colorado Boulder (US)
Corresponding author: Collins, Allan C.
ORCID: Marks, Michael J.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 1994-04
Volume: 62
Issue: 4
Pages: 1390-1398
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1046/j.1471-4159.1994.62041390.x
OpenAlex: W2030003339
Cited by: 126
References: 33
Citations by year: 2022: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 2
FWCI: 4.44
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5202 d)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01aa006391-07)
National Institute on Alcohol Abuse and Alcoholism (AA 06391)
National Institute on Drug Abuse (DA 03194, NIDA DA-00116, R01DA003194)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords: nicotinic receptor desensitization, nicotine, dopamine release, striatal synaptosomes, receptor recovery, Hill coefficient, mouse striatum
MeSH terms: Animals, Corpus Striatum, Dopamine, Dose-Response Relationship, Drug, Drug Tolerance, Female, Kinetics, Mice, Inbred C57BL, Nicotine, Receptors, Nicotinic, Synaptosomes, Tritium, Mice

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Desensitization of Nicotine‐Stimulated [3H]Dopamine Release from Mouse Striatal Synaptosomes

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