Correction of neuroleptic-induced parkinsonism in rats with two central cholinoblockers atropine and pentifine (acetylene aminoalcohol synthesized at Institute of Toxicology) were studied by measuring the content of acetylcholine in the striatum. The content of the transmitter secretion was estimated from the content of bound acetylcholine fraction in homogenates of the above-mentioned compartment of the brain. The results indicate that atropine and pentifine in doses equally effectively preventing catalepsy in rats had different effects on acetylcholine secretion in the striatum. Hence, cholinolytics with different pharmacological selective effects differently interact with central muscarine receptor subtypes.
Pre-and postsynaptic M-cholinergic receptors are typified by radioligand analysis with selective cholinoblockers by comparing ligand binding in homogeneous and synaptosomal fractions of different structures of rat brain. It is found that presynaptic receptors of the hemispheres belong to M 3 subtype and those of the brain stem are probabl,y of M 4 subtype.
Key Words: presynapsis; muscarinic cholinergic receptors; heterogeneityThe effect of cholinotropic drugs on the tonicity of cholinergic innervation depends on the sum of its influences at the pre-and postsynaptic levels. Therefore, the type of pre-and postsynaptic Mcholinergic receptors (M-ChR) in different structures of the central nervous system (CNS) is important for understanding the mechanisms of action of selective cholinergic agonists and antagonists and for synthesis and screening of highly specific cholinergic drugs.In the present study we used the synaptosome fraction as an object enriched with presynaptic MChR in comparison with homogenate of the correspondent brain structure.Our objective was to demonstrate the possibility of using the proposed approach for typifying preand postsynaptic M-ChR in the brain hemisphere and stem.
MATERIALS AND METHODSExperiments were carried out on female rats weighing 180-220 g. The synaptosomal fraction was isolated by the classical method [1,2]. The affinity of cholinergic antagonists for M-ChR was determined Institute of Toxicology, Ministry of Health of Russia, St. Petersburg by the method of radioligand analysis using 3H-quinuclidinyl benzilate (Amersham) with a specific activity of 37 Ci/mmol. The experimental procedure was based on the method described elsewhere [3]. The selective cholinoblockers pirenzepine and hexahydroxyladiphenidol were resynthesized, and SL-2, a tetra-amine M2-selective cholinoblocker, was synthesized at the Institute of Toxicology. These cholinoblockers were used as test ligands. Radioactivity was measured in a Mark-III scintillation counter using the standard dioxane scintillator. Data processing, calculation of competitive inhibition constant (K), and percentage of receptors with high (Bh) and low (B~) affinity for the test ligands were performed by nonlinear regression analysis using specially designed software.
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