Receptors In Mouse Brain Research Articles

Regulation of opiate receptors in mouse brain: arcuate nuclear lesion induces receptor up-regulation and supersensitivity to opiates

Lesion of the hypothalamic arcuate nucleus of the mouse by neonatal application of monosodium glutamate (MSG) increased the binding of [ 3H]dihydromorphine to membranes prepared from the midbrain. A saturation curve of [ 3H]dihydromorphine binding indicated that MSG increased the number of the opiate receptors. The MSG-treated mice also exhibited an enhanced response to morphine and naltrexone regarding thermal pain sensitivity. The physiological implications of opiate receptors up-regulations upon arcuate nuclear lesion are discussed.

Identification of beta-adrenergic receptors in mouse brain with 3H-dihydroalprenolol.

Recently, β-adrenergic receptor binding has been measured in the brains of various animals by direct receptor binding technic. However, the procedure slightly differs for each animal even among the same species. We tried to characterize β-adrenergic receptor binding in a mouse pallium using 3H-dihydroalprenolol (DHA) as radioligand. The results are as follows (1) 3H-DHA binds to the tissue suspension from mouse pallium in a time dependent manner, but this binding rapidly attains plateau, (2) β-adrenergic agonists and antagonist compete for 3H-DHA binding sites in the same order with known affinity for β-adrenergic receptor, and (3) binding is fully saturated, with high affinity and stereoselectivity for an adrenergic agonist. These findings indicate that 3H-DHA specific binding sites represent the β-adrenergic receptors. We concluded that it is possible to identify the β-adrenergic receptor in mouse pallium applying almost the same conditions as for rat.

Alterations of brain cholecystokinin receptors in mice made obese with goldthioglucose.

Abstract: We investigated the binding of cholecystokinin (CCK) to its receptors in brains of mice made obese by the injection of goldthioglucose. In these mice there was a significant increase in the number of binding sites in cerebral cortex, hypothalamus, and olfactory lobes in comparison with either unin‐jected mice or injected mice that did not become obese. The present study demonstrates, therefore, that obesity in mice is associated with changes in brain CCK receptors, and raises the possibility that obesity in certain animals may be related to abnormalities in the binding of CCK to its receptors.

Effect of procarbazine on benzodiazepine receptor in mouse brain

Proearbazine, a non-benzodiazepine tranquilizer and anti-convulsant, significantly decreased the binding of [ 3H]diazepam to mouse cerebellar membranes. The drug treatment reduced both the affinity and density of the receptor. The effect, however, was more pronounced on the number of binding sites suggesting occupation of the receptor by procarbazine. The results suggest that benzodiazepine receptors may also be involved in the pharmacological action of non-benzodiazepine drugs.

Strain differences in opiate receptors in mouse brain

Various opiate ligands were bound to brain membranes of mice of the Recombinant Inbred System. The specific binding of low levels of [ 3H]naloxone, [ 3H]dihydromorphine and [ 3H]ethylketocyclazocine was distributed in a similar fashion among the inbred strains, and in a pattern different from that observed for [ 3H](D-Ala 2, D-Leu 5)-enkephalin. The results indicate that the inbred strains differ in μ- and δ-type binding and support the concept of multiple opiate receptors in mouse brain.

Altered ontogenesis of muscarinic cholinergic receptor in mouse brain: effect of L-thyroxine and betamethasone.

The effects of L-T4 and betamethasone treatment of newborn mice on the development of the cholinergic muscarinic receptor in certain brain regions was studied using the potent labeled muscarinic antagonist [3H]4-N-methyl-piperidyl benzilate. Treatment with both L-T4 and betamethasone caused an accelerated accumulation of muscarinic receptors in the cortex 16 days post partum, with a subsequent reduction in level at 30 days. In the cerebellum and caudate putamen, only betamethasone caused a similar early accumulation of muscarinic receptors, while the later effect, namely a reduction in the level at 30 days, was seen with both hormones in these two regions as well as in the hippocampus. The results can explain some behavioral effects observed in other studies after treatment with these hormones.

Cholinergic receptor loss in brains of aging mice

The number of synaptic cholinergic receptors in brains of mice decreases with aging after 18 months. Alterations in body weight, starvation, and circadian variations could not account for these changes. The decrease in receptors was not associated with significant changes in receptor affinity and brain protein and DNA and RNA content. The determination of postsynaptic cholinergic receptor density is a quantitative chemical correlate of aging of the rodent brain. Whether or not the declining receptor density is a cause of the age-related decline of learning behavior can be resolved by observing the effects of manipulations of receptor density on learning in animals.

Chronic ethanol feeding produces an increase in muscarinic cholinergic receptors in mouse brain

Chronic ethanol administration (seven days) to mice produces physical dependence while subsequent withdrawal produces seizures and convulsions, especially during the first 24 hours. It is known that ethanol can inhibit brain acetylcholine (ACh) release. Our present study suggests that hippocampal (+25%) and cortical (+14%), but not striatal neurons, can respond to the ethanol-induced reduction in neurotransmitter (ACh) availability by increasing the number of muscarinic cholinergic receptors. It is possible that these supersensitive neurons are involved in the CNS hyperexcitability induced by withdrawal from chronic ethanol.

Muscarinic binding to mouse brain receptor sites

In mouse brain the binding of [ 3H]-Atropine to the muscarinic receptor seems to be a simple mass-action determined process as gauged both by approach to equilibrium kinetics and binding at equilibrium. In contrast, using isotopic dilution technique, dissociation measurements indicate the existence of two receptor-ligand complexes. It would appear that association and dissociation rates of binding of the muscarinic antagonists atropine, scopolamine, N-methyl-4-piperidyl benzilate (4NMPB) and 3-quinuclidinyl benzilate (QNB) decrease with increasing affinity based on comparisons of kinetic binding data. The differences between the association rate constants are small whereas those between the dissociation rate constants differ markedly. This kinetic behavior is similar to the well-known time profile of antimuscarinic activity in isolated tissues. These phenomena are discussed in terms of possible isomerization of the receptor-ligand complex, as has been proposed recently for [ 3H]-scopolamine and [ 3H]-4NMPB binding.

Rapid and dissociated changes in sensitivities of different dopamine receptors in mouse brain

DOPAMINERGIC systems in various parts of the mammalian brain, particularly in striatal, mesolimbic, mesocortical and hypothalamic structures, are involved in the control of motor activity, autonomic processes and emotional behaviour. An altered dopaminergic transmission in striatum seems to be responsible for Parkinsonism, whereas abnormalities in other, still poorly defined, dopaminergic synapses could participate in the aetiology of schizophrenia1–3. Thus, there is considerable theoretical as well as therapeutical interest in defining specific characteristics of different dopaminergic systems participating in the control of these various functions.

The acetylcholine receptor: Isolation of a brain nicotinic receptor and its preliminary characterization in lipid bilayer membranes

The technique of affinity chromatography with the curarizing neurotoxins of Naja naja venom has been employed to extract nicotinic acetylcholine receptors from the brain tissues of mouse and hog. Both carbochol and hexamethonium were used as linear or step gradients to elute the receptor and its properties were investigated in lipid bilayer membranes. Of particular interest is the observation that discrete quanta of conductance could be observed across an NaCl gradient of 1.0:0.1 M. By switching the voltage-clamp across the bilayer between a positive and negative 80 mV, the separate Na + and Cl − conductances of these quanta could be estimated and the following conductances of the smallest discrete quanta were observed: 3.7 · 10 −11 Ω −1 (Na +) and 5.9 · 10 −11 Ω −1 (Cl −) for mouse brain receptors; 3.8 · 10 −11 Ω −1 (Na +) and 4.7 · 10 −11 Ω −1 (Cl −) for hog brain receptors. Large aggregates of receptors appeared to activate and deactivate as multiples of a basic conductance size, although there is evidence that they may not represent the actual gating of ion channels. A “background noise” that is not within the temporal capability of the recording system is also present at an intensity that seems to parallel the number of activated receptors, and in view of recent electrophysiological evidence that the relaxation lifetime of the open channel state is of a millisecond duration, it may be that this “noise” actually represent the channel gating.