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Ligand specificity of nicotinic acetylcholine receptors in rat spinal cord: studies with nicotine and cytisine.
J Pharmacol Exp Ther. 1994 Jul; 270(1):159-66.JP

Abstract

Administration of nicotinic agonists to the spinal cord leads to a variety of cardiovascular and behavioral responses. The discrete localization of afferent and efferent fibers presents a system in which occupation of nicotinic receptor subtypes might be correlated with specific pharmacologic responses. To this end, we examined [3H]cytisine and [3H]nicotine binding to membranes isolated from regions of the rat spinal cord. [3H]Cytisine showed saturable, noncooperative (nH congruent to 1) binding to a single-class of sites with a Kd of 0.44 +/- 0.01 nM and total saturable sites of 19.9 +/- 0.9 fmol/mg of protein. [3H]Cytisine binding to membranes from intermediolateral cell column and dorsal and ventral sections of the lumbosacral regions each revealed a single class of binding sites with virtually identical Kd values. However, the dorsal sections of the lumbar spinal cord contained a higher number of total binding sites than ventral lumbar or intermediolateral sections. The rank order potencies of the nicotinic agonists competing for [3H]cytisine binding was cytisine > I-nicotine > N-methylcarbamylcholine > dimethylphenylpiperazinium > acetylcholine > d-nicotine > carbamylcholine. Competitive antagonists also competed with high affinities (Ki as low as nanomolar) with the order of potencies being alpha-lobeline > or = dihydro-beta-erythroidine >> methyllycaconitine, whereas the channel blockers, mecamylamine and hexamethonium, only competed at concentrations > or = 100 microM. Competitive ganglionic blockers such as d-tubocurarine or trimethaphan and neurotoxins such as alpha-bungarotoxin, alpha-cobratoxin or neuronal bungarotoxin had weak affinities for cytisine sites. Similar to [3H]cytisine, [3H]nicotine also revealed a saturable single class of binding sites, but of lower affinity. The rank order of Ki values of the agonists, antagonists and neurotoxins for competing with [3H]nicotine binding was similar to the order for [3H]cytisine. Nicotinic receptors in the spinal cord membrane show a specificity for both agonists and antagonists that differ from neuronal receptors in the ganglia or the regions of the brain characterized to date. These findings, when correlated with the pharmacological responses documented in the comparison article suggests that the spinal nicotinic receptors may define a new member of the neuronal nicotinic receptor family.

Authors+Show Affiliations

Department of Pharmacology, University of California, San Diego, La Jolla.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8035312

Citation

Khan, I M., et al. "Ligand Specificity of Nicotinic Acetylcholine Receptors in Rat Spinal Cord: Studies With Nicotine and Cytisine." The Journal of Pharmacology and Experimental Therapeutics, vol. 270, no. 1, 1994, pp. 159-66.
Khan IM, Yaksh TL, Taylor P. Ligand specificity of nicotinic acetylcholine receptors in rat spinal cord: studies with nicotine and cytisine. J Pharmacol Exp Ther. 1994;270(1):159-66.
Khan, I. M., Yaksh, T. L., & Taylor, P. (1994). Ligand specificity of nicotinic acetylcholine receptors in rat spinal cord: studies with nicotine and cytisine. The Journal of Pharmacology and Experimental Therapeutics, 270(1), 159-66.
Khan IM, Yaksh TL, Taylor P. Ligand Specificity of Nicotinic Acetylcholine Receptors in Rat Spinal Cord: Studies With Nicotine and Cytisine. J Pharmacol Exp Ther. 1994;270(1):159-66. PubMed PMID: 8035312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ligand specificity of nicotinic acetylcholine receptors in rat spinal cord: studies with nicotine and cytisine. AU - Khan,I M, AU - Yaksh,T L, AU - Taylor,P, PY - 1994/7/1/pubmed PY - 1994/7/1/medline PY - 1994/7/1/entrez SP - 159 EP - 66 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 270 IS - 1 N2 - Administration of nicotinic agonists to the spinal cord leads to a variety of cardiovascular and behavioral responses. The discrete localization of afferent and efferent fibers presents a system in which occupation of nicotinic receptor subtypes might be correlated with specific pharmacologic responses. To this end, we examined [3H]cytisine and [3H]nicotine binding to membranes isolated from regions of the rat spinal cord. [3H]Cytisine showed saturable, noncooperative (nH congruent to 1) binding to a single-class of sites with a Kd of 0.44 +/- 0.01 nM and total saturable sites of 19.9 +/- 0.9 fmol/mg of protein. [3H]Cytisine binding to membranes from intermediolateral cell column and dorsal and ventral sections of the lumbosacral regions each revealed a single class of binding sites with virtually identical Kd values. However, the dorsal sections of the lumbar spinal cord contained a higher number of total binding sites than ventral lumbar or intermediolateral sections. The rank order potencies of the nicotinic agonists competing for [3H]cytisine binding was cytisine > I-nicotine > N-methylcarbamylcholine > dimethylphenylpiperazinium > acetylcholine > d-nicotine > carbamylcholine. Competitive antagonists also competed with high affinities (Ki as low as nanomolar) with the order of potencies being alpha-lobeline > or = dihydro-beta-erythroidine >> methyllycaconitine, whereas the channel blockers, mecamylamine and hexamethonium, only competed at concentrations > or = 100 microM. Competitive ganglionic blockers such as d-tubocurarine or trimethaphan and neurotoxins such as alpha-bungarotoxin, alpha-cobratoxin or neuronal bungarotoxin had weak affinities for cytisine sites. Similar to [3H]cytisine, [3H]nicotine also revealed a saturable single class of binding sites, but of lower affinity. The rank order of Ki values of the agonists, antagonists and neurotoxins for competing with [3H]nicotine binding was similar to the order for [3H]cytisine. Nicotinic receptors in the spinal cord membrane show a specificity for both agonists and antagonists that differ from neuronal receptors in the ganglia or the regions of the brain characterized to date. These findings, when correlated with the pharmacological responses documented in the comparison article suggests that the spinal nicotinic receptors may define a new member of the neuronal nicotinic receptor family. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8035312/Ligand_specificity_of_nicotinic_acetylcholine_receptors_in_rat_spinal_cord:_studies_with_nicotine_and_cytisine_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8035312 DB - PRIME DP - Unbound Medicine ER -