Nicotine-like Binding Sites Research Articles

Action of protein kinase inhibitors on calcium current in intestinal smooth muscle cells

Immature (10 days of age) and adult (60 days of age) mice were given a single peroral administration of 0.5 mg p,p'-DDT/kg body wt. or a fat emulsion vehicle. The mice were killed 24 h or 7 days post-treatment and the muscarine- and nicotine-like binding sites were measured in the cerebral cortex and in the cerebellum using [3H]quinuclidinyl benzilate ([3H]QNB) and [3H]α-bungarotoxin ([3H]α-BTX), respectively, as ligands. A significant decrease in the [3H]QNB binding to the muscarine-like receptors in the cerebral cortex was seen in the 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT)-treated adults after 7 days. The effects on the muscarine-like receptors appeared to be different in the immature mice compared to the adults, showing an increase between 24 h and 7 days post-treatment in the immature and a decrease in the adults. No change was seen on the nicotine-like receptors.

3H]methylcarbamylcholine, a new radioligand for studying brain nicotinic receptors

A new radioligand, [ 3H]methylcarbamylcholine, has been developed for the study of the nicotinic cholinergic and nicotine-like binding sites in rat brain membranes. A Scatchard analysis with the radioligand yielded a K d of 1.1 × 10 −9M and a B max of 4.0 × 10 −14 moles/mg protein which compares with a lower affinity site for (−)-[ 3H]nicotine having a K d of 3 × 10 −9M and a B max of 2 × 10 −14 moles/mg. Comparable values for the K d were obtained from a Hill plot and from calculations based on rate constants for association and dissociation. A comparison of the binding affinities of various nicotine analogues, nicotinic cholinergic agents, and other neurotropic agents revealed a close similarity between the two radioligands, with the exception that quaternization of nicotine or carbamate esters increased affinity by at least an order of magnitude with [ 3H]methylcarbamylcholine and resulted in a comparable decrease in affinity with [ 3H]nicotine as the ligand. The binding of [ 3H]methylcarbamylcholine, like [ 3H]nicotine, was not displaceable by muscarinic cholinergic antagonists. It was concluded that, although [ 3H]methylcarbamylcholine and [ 3H]nicotine bind to a common receptor in brain, the functional and chemical characteristics of the receptor(s) differ in some respects from peripheral nicotinic cholinergic receptors.

Regional [3H]acetylcholine and [3H]nicotine binding in developing mouse brain

The postnatal development of nicotine-like binding sites in the cortex, hippocampus, midbrain and cerebellum of 3-, 7-, 12-, 17- and 30-day-old mice was studied. Two different nicotinic cholinergic ligands, namely [3H]acetylcholine ([3H]ACh) and [3H]nicotine ([3H]NIC) were used to detect the nicotine-like binding sites in in vitro binding assays. The postnatal development of the binding sites of [3H]NIC increased gradually with age in all brain regions studied. The [3H]ACh binding, on the other hand, showed a marked peak on day 12 in the cerebellum and midbrain but did not change notably with age in the hippocampus and cortex, except for a slight temporary increase in the cortex on day 7. The time-course for the appearance of nicotinic binding sites as observed with [3H]ACh was found to be rather similar to that earlier described for [3H]alpha-bungarotoxin binding sites, whereas that for [3H]NIC differed from that described for other nicotinic ligands.

Development of nicotine-like binding sites in discrete areas of mouse brain — a study using labelled nicotine and different nicotinic antagonists as receptor ligands

International Journal of Developmental NeuroscienceVolume 3, Issue 4 p. 473-473 Cholinergic System Development of nicotine-like binding sites in discrete areas of mouse brain — a study using labelled nicotine and different nicotinic antagonists as receptor ligands A. Nordberg, A. Nordberg Dep of Pharmacology, University of Uppsala, National Pood Administration, Uppsala, SwedenSearch for more papers by this authorC. Larsson, C. Larsson Dep of Pharmacology, University of Uppsala, National Pood Administration, Uppsala, Sweden Toxicology Laboratory, National Pood Administration, Uppsala, SwedenSearch for more papers by this authorY. Falkeborn, Y. Falkeborn Toxicology Laboratory, National Pood Administration, Uppsala, SwedenSearch for more papers by this authorP. Slanina, P. Slanina Toxicology Laboratory, National Pood Administration, Uppsala, SwedenSearch for more papers by this author A. Nordberg, A. Nordberg Dep of Pharmacology, University of Uppsala, National Pood Administration, Uppsala, SwedenSearch for more papers by this authorC. Larsson, C. Larsson Dep of Pharmacology, University of Uppsala, National Pood Administration, Uppsala, Sweden Toxicology Laboratory, National Pood Administration, Uppsala, SwedenSearch for more papers by this authorY. Falkeborn, Y. Falkeborn Toxicology Laboratory, National Pood Administration, Uppsala, SwedenSearch for more papers by this authorP. Slanina, P. Slanina Toxicology Laboratory, National Pood Administration, Uppsala, SwedenSearch for more papers by this author First published: 1985 https://doi.org/10.1016/0736-5748(85)90230-8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume3, Issue41985Pages 473-473 RelatedInformation

Effects of ddt on muscarine- and nicotine-like binding sites in cns of immature and adult mice

Immature (10 days of age) and adult (60 days of age) mice were given a single peroral administration of 0.5 mg p, p'-DDT/kg body wt. or a fat emulsion vehicle. The mice were killed 24 h or 7 days post-treatment and the muscarine- and nicotine-like binding sites were measured in the cerebral cortex and in the cerebellum using [ 3H]quinuclidinyl benzilate ([ 3H]QNB) and [ 3H]α-bungarotoxin ([ 3H]α-BTX), respectively, as ligands. A significant decrease in the [ 3H]QNB binding to the muscarine-like receptors in the cerebral cortex was seen in the 1,1,1-trichloro-2,2- bis( p-chlorophenyl)ethane (DDT)-treated adults after 7 days. The effects on the muscarine-like receptors appeared to be different in the immature mice compared to the adults, showing an increase between 24 h and 7 days post-treatment in the immature and a decrease in the adults. No change was seen on the nicotine-like receptors.

A comparison of the regional ontogenesis of nicotine- and muscarine-like binding sites in mouse brain

The postnatal development of the cholinergic neurotransmitter system was studied in the cortex, hippocampus, midbrain and cerebellum of 3-, 7-, 12-, 17- and 30-day-old NMRI mice. The concentration of muscarine-like binding sites determined with [3H]quinuclidinyl benzilate as a ligand increased progressively with age. A similar developmental pattern was found for the activity of a presynaptic marker, choline acetyltransferase (ChAT). When expressed as a percentage of the values for 30-day-old mice, however, the muscarine-like receptors were parallel but preceding the development of ChAT in all the brain regions studied. The concentration of nicotine-like binding sites studied with [3H]α-bungaro-toxin as a ligand gradually increased with age in the cortex, hippocampus and midbrain, with a peak between days 7 and 12, followed by a decrease towards day 30. With [3H]tubocurarine as a ligand, on the other hand, the concentration of nicotine-like binding sites was in general high at 3 days and gradually decreased with age, suggesting that different subpopulations of nicotine-like receptors might be determined when the two ligands are used.

Changes in cholinergic activity in human hippocampus following chronic alcohol abuse

Cholinergic mechanisms in the hippocampus seem to play a role in memory function. Since it is well known that chronic alcoholics often have a disturbed memory function, the cholinergic activity of the hippocampus has been measured in 20 chronic alcoholics and 14 controls, post-mortem. Of the alcoholics, 13 were classified as “intoxicated” alcoholics and 7 as “sober” alcoholics, i.e., without ethanol in blood or urine at the time of death. A lower, although not significantly lower activity of the enzyme choline acetyltransferase (ChAT, presynaptic marker) was measured in the hippocampus of the chronic alcoholics as compared to the control group. A trend towards a lower number of muscarine-like binding sites was also observed for the alcoholic group, but was only significant for the oldest group of alcoholics (59–68 years; −30%; p<0.01) in comparison to controls. No significant change in the number of nicotine-like binding sites was found. A normal aging process with degenerative nerve cell changes might, in combination with an excessive intake of ethanol, lead to the more pronounced decrease in muscarine-like binding sites found for the older alcoholics.

Changes in populations of cholinergic binding sites in brain after chronic exposure to barbital in rats

Male rats were treated with barbital in their drinking fluid for about 40 weeks (daily dose 200 mg/kg). The treatment was stopped on day 0 and the number of muscarinic binding sites was measured in 3 brain parts (striatum; cortex and hippocampus; medulla oblongata and midbrain) during the abstinence with labeled quinuclidinyl benzilate (QNB) as ligand. Nicotine-like binding sites were quantified in the cortex with labeled tubocurarine. An increased number of QNB-binding sites was found in the striatum during the early part of the abstinence (days 0–3), followed by another increase later in the abstinence (days 12–21). In the cortex preparation a variable increase in QNB binding was measured from days 2–9 of the abstinence, whereas in the midbrain preparation the QNB binding was found to be increased only on day 9 in comparison to controls. A change in the proportion between high and low affinity muscarinic binding sites (measured by agonist-antagonist competition) was found in the cortex preparation during the period when the QNB binding was increased. Prior to the maximum abstinence convulsions the QNB binding was higher in rats without recorded spontaneous convulsions in comparison to rats with convulsions. A negative correlation between the time after the last convulsion and the number of QNB binding sites was observed in data from rats where the maximum convulsions had occurred before sacrifice. In addition, a negative relationship between the number of muscarine- and nicotine-like binding sites was found in the cortex during days 5–9 of the abstinence.

Cholinergic receptors in human hippocampus-- regional distribution and variance with age

The anterio-posterior distribution of cholinergic receptor binding sites in human hippocampus (five parts) as well as the effect of age (age range 3 days - 85 years) on receptor properties has been studied. Muscarinic binding sites was measured using labelled quinuclidinyl benzilate ( 3H-QNB) as ligand and labelled tubocurarine ( 3H-TC) was used for measurement of nicotine-like binding sites. The highest number of 3H-QNB binding sites in human hippocampus was measured at 3 days and 3 weeks of age and the lowest at 82 years of age. The proportion of high and low affinity muscarinic binding sites respectively was about the same at all ages investigated. A decrease in 3H-QNB binding sites with age was found in the anterior parts of the hippocampus (age range 55–84 years). When individual data for number of 3H-TC binding sites were plotted against corresponding number of 3H-QNB binding sites a strong correlation was observed in most of the different regions of the hippocampus.

Chronic nicotine exposure in rat: A behavioural and biochemical study of tolerance

Rats received nicotine (50 mg nicotine base/1) in their drinking fluid for 28 days. The daily consumption of nicotine was about 4 mg/kg per day. Controls received plain water. Body weight, food consumption and fluid intake were registered during the whole treatment period and up to 31 days after withdrawal of nicotine. A significant lower body weight was noted in rats, treated with nicotine, in comparison with control rats during the whole treatment period. After withdrawal of nicotine the body weight returned to normal. Only slight effects were seen on the food intake (at the beginning of the nicotine treatment). The fluid intake, on the other hand, was significantly lower in the nicotine group during the whole period of treatment and a reduced intake persisted 28 days after withdrawal of nicotine. Tolerance to nicotine was measured in rats 24 hours after withdrawal of nicotine, using two behavioural tests. No tolerance to nicotine was found after 31 days of withdrawal of nicotine. The number of nicotine-like binding sites was found to be reduced in the midbrain 24 hours after withdrawal of nicotine, while no significant change was found in the cortex and hippocampus.