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Biomedical subjects

M Sokolovsky

Publications and source records attributed to M Sokolovsky.

At least 145 records · Page 8Linked to original sources
PubMed1981

Molecular regulation of receptors: interaction of beta-estradiol and progesterone with the muscarinic system.

The effects of various substrates on the binding of agonists to muscarinic receptors were studied in the rat hypothalamus and adenohypophysis by competition experiments using the highly specific tritiated muscarinic antagonist N-methyl-4-piperidyl benzilate. It was found that agonist binding properties were affected only by the steroid sex hormones (beta-estradiol and progesterone), both of which resulted in a decrease in the proportion of high-affinity binding sites and a decrease in the dissociation constant. This suggests a link between the muscarinic system and the mechanism by which these steroids exert their gonadotropin-releasing effect on the adenohypophysis. We propose a model to depict the putative relationship between the muscarinic system and other receptor systems, including that which controls the steroid sex hormones.

Animals↗
PubMed1981

Studies on muscarinic receptors in mouse and rat hypothalamus: a comparison of sex and cyclical differences.

The ligand binding properties of muscarinic receptors present in whole hypothalamus as well as in its three regions (preoptic area, median and posterior regions) were studied in male rats and mice, as well as in female rats during various stages of the estrous cycle, using the tritiated antagonist N-methyl-4-piperidyl benzilate. Kinetic and equilibrium analysis of antagonist binding as well as competition experiments with agonists, were used to probe the nature of the binding sites and possible differences between specific muscarinic sites in the various preparations. We could detect differences in agonist binding parameters between male and female rats in the preoptic area. In female rats binding of agonist to high affinity state is characterized by a lower affinity (27 nM) than in males (3.7 nM). Secondly, the population of agonist high affinity sites at the proestrous stage is much higher than that at other stages of cycle (66 vs. 38%). In addition, the binding properties of muscarinic receptors following intracisternal 6-hydroxydopamine lesion were investigated. This treatment resulted in a decrease of about one sixth of the total muscarinic receptors in the hypothalamus. The data are best interpreted as a degeneration of existing presynaptic muscarinic receptors located on catecholamine terminals in the hypothalamus. The pre- and postsynaptic nature of the muscarinic receptors, their localization in view of their binding properties, and their possible physiological role are discussed.

Animals↗
PubMed1981

Biochemical characterization and sex dimorphism of muscarinic receptors in rat adenohypophysis.

The ligand binding properties of muscarinic receptors present in rat adenohypophysis were studied using the tritiated antagonists N-methyl-4-piperidyl benzilate, 3-quinuclidinyl benzilate, and methylscopolamine. Equilibrium analysis of antagonists binding as well as competition experiments with several agonists were used to probe the nature of binding sites. The nature of antagonist binding in the adenohypophysis points to heterogeneity of binding sites, in contrast to other brain regions, in which homogeneous populations of muscarinic receptors were detected. Some of the binding properties, e.g. affinity constants, population of high affinity agonist binding sites, etc., clearly indicated differences between male and female rats as well as differences in female rats at various stages of estrous cycle. The nature of these receptors and their possible physiological role are discussed.

Animals↗
PubMed1981

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.

Aging↗
PubMed1980

Amitriptyline: long-term treatment elevates alpha-adrenergic and muscarinic receptor binding in mouse brain.

The effects of long-term treatment of the tricyclic antidepressant drug, amitriptyline, on alpha-adrenergic, muscarinic and dopaminergic receptor binding were studied in mouse brain. No changes could be observed after 7 or 14 days of amitriptyline administration, but after 21 days a two-fold increase in alpha-adrenergic binding was detected in the medulla pons and in the hippocampus using [3H]WB-4101 as the binding ligand. In the same two regions, a moderate increase in muscarinic receptor binding (25%) as measured by [3H]4NMPB was seen, while no change was detected in dopaminergic receptor binding measured by [3H]spiperone. Scatchard analysis reveals that the increases in receptor densities are not a result of changes in the dissociation constants of the tritiated drugs for their receptors. It is suggested that the increase in alpha-adrenergic as well as in muscarinic binding is a consequence of a chronic blockade of these two types of receptors by amitriptyline in vivo.

Adrenergic alpha-Antagonists↗
PubMed1980

Characterization of the presynaptic muscarinic receptor in synaptosomes of Torpedo electric organ by means of kinetic and equilibrium binding studies.

The ligand binding properties of presynaptic muscarinic receptors present in purified synaptosomal fraction isolated from the electric organ of Torpedo have been studied, using the specific tritiated antagonist N-methyl-4-piperidylbenzilate ([3H]-4NMPB). Direct and competition binding studies revealed that antagonists bind with high affinity to the presynaptic receptor, with saturability occurring at very low ligand concentration, in a stereospecific manner, and according to a simple mass action law. The kinetic results for [3H]4NMPB binding could best be fitted by a two-step sequential isomerization model. The affinities of both agonists and antagonists decreased as a function of increasing ionic strength. Analysis of agonist binding was performed according to the two-site model suggested by Birdsall and Hulme. Varying the buffer conditions resulted in changes both in the affinities of the agonist for the two agonist sites and in their relative proportions. For a given buffer composition the proportion of high and low affinity sites is constant, but agonists affinities decrease as a function of increase in ionic strength. The finding that at a given ionic strength the proportion of high and low affinity agonist sites can be manipulated suggests that agonist binding sites in Torpedo receptor may interconvert. The apparent dissociation constants measured in Torpedo physiological buffer for both agonists and antagonists are in the same range as the concentrations affecting synaptosomal ACh release. The affinity of agonists towards the presynaptic muscarinic Torpedo receptor was found to be higher than their affinity towards the postsynaptic muscarinic receptor, e.g. in cat and rabbit irides, mouse cortex, etc., and closely resembles the affinity in mouse medulla pons. The localization of pre- and postsynaptic muscarinic receptors in view of their different binding properties is discussed.

Acetylcholine↗
PubMed1980

Biochemical characterization of muscarinic receptors.

Characteristics of the binding mechanism to specific muscarinic sites were determined by means of high affinity binding of tritium labeled N-methyl-4-piperidylbenzilate (4-NMPB) to homogenate from various regions of mouse brain: cortex, caudate putamen, thalamus, hippocampus, medulla pons and cerebellum. In vivo experiments confirm results obtained when investigating regional distribution of the muscarinic receptors in vitro. Kinetics as well as equilibrium analysis of the binding in the different brain regions to probe the nature of the binding is described. The combined data strongly support the conclusion that mouse brain exhibits functional heterogeneity of muscarinic receptors.

Animals↗
PubMed1980

On the regulation of acetylcholine release: a study utilizing Torpedo synaptosomes and synaptic vesicles.

1. Addition of ATP to isolated highly purified Torpedo synaptic vesicles results in 45Ca2+ uptake. 2. Ca2+ dependent ACh release from Torpedo synaptosomes is accompanied by the phosphorylation of a specific protein with an apparent subunit molecular weight of about 100,000 (band alpha). 3. Activation of the presynaptic muscarinic receptors by an agonist inhibits Ca2+-dependent ACh release from Torpedo synaptosomes. This process seems to be mediated through an interference with the phosphorylation of the band alpha protein, and not by blocking the voltage-dependent presynaptic Ca2+ channel.

Acetylcholine↗