Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02427 (Atropine)
 3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using immunohistochemical methods, choline acetyltransferase and vasoactive intestinal polypeptide immunoreactive (ChAT-I and VIP-I) fine fibers with varicosity-like structures were observed in the rat and cat cerebral arteries. Acetylcholine (ACh) induced dual responses in endothelium-intact internal carotid arteries of the cat; it induced vasodilation at low concentrations and constrictions at high concentrations (greater than 10(-6) M). ACh induced contraction exclusively in endothelium-rubbed preparations. Atropine (10(-7) M) blocked ACh-induced constriction and dilatation. ACh-induced vasodilation was potentiated by M & B 22,948 (2 x 10(-5) M), a selective cyclic GMP phosphodiesterase inhibitor. Vasoconstriction induced by ACh was inhibited by neomycin (3 x 10(-3) M), an inositol phosphate synthesis inhibitor, which did not affect the neuropeptide Y-induced contraction. VIP-induced dilation of the cat internal carotid arteries was not affected by removing the endothelial layer, but was blocked by VIP receptor antagonist ([Ac-Tyr1, D-Phe2]-GRF 1-29 amide) and potentiated by cilostazol (2 x 10(-5) M), a selective cyclic AMP phosphodiesterase inhibitor. These results are consistent with previous findings that cerebral blood vessels receive cholinergic and VIP-ergic innervations, and that ACh-induced endothelium-dependent vasodilation is mediated by cyclic GMP synthesis, and that VIP-induced endothelium-independent vasodilation is mediated by cyclic AMP synthesis. The present study, however, demonstrates for the first time the presence of varicosity-like structure associated with ChAT-I fibers, suggesting the presence of cholinergic nerve terminals and that ACh-induced cerebral vasoconstriction is mediated by phosphatidyl-inositide turnover.
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PMID:VIP-ergic and cholinergic innervations in internal carotid arteries of the cat and rat. 172 Aug 37

The role of acetylcholine receptors in the control of chick myoblast fusion in culture has been explored. Spontaneous fusion of myoblasts was inhibited by the nicotinic acetylcholine receptor antagonists alpha-bungarotoxin, Naja naja toxin and monoclonal antibody mcAb 5.5. The muscarinic antagonists QNB and n-methyl scopolamine were without effect. Atropine had no effect below 1 microM, where it blocks muscarinic receptors; at higher concentrations, when it blocks nicotinic receptors also, atropine inhibited myoblast fusion. The inhibitions imposed by acetylcholine receptor antagonists lasted for approximately 12 h; fusion stimulated by other endogenous substances then took over. The inhibition was limited to myoblast fusion. The increases in cell number, DNA content, the level of creatine phosphokinase activity (both total and muscle-specific isozyme) and the appearance of heavy chain myosin, which accompany muscle differentiation, followed a normal time course. Pre-fusion myoblasts, fusing myoblasts, and young myotubes specifically bound labeled alpha-bungarotoxin, indicating the presence of acetylcholine receptors. The nicotinic acetylcholine receptor agonist, carbachol, induced uptake of [14C]Guanidinium through the acetylcholine receptor. Myoblasts, aligned myoblasts and young myotubes expressed the synthetic enzyme Choline acetyltransferase and stained positively with antibodies against acetylcholine. The appearance of ChAT activity in myogenic cultures was prevented by treatment with BUDR; nonmyogenic cells in the cultures expressed ChAT at a level which was too low to account for the activity in myogenic cultures. We conclude that activation of the nicotinic acetylcholine receptor is part of the mechanism controlling spontaneous myoblast fusion and that myoblasts synthesize an endogenous, fusion-inducing agent that activates the nicotinic ACh receptor.
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PMID:A role for acetylcholine receptors in the fusion of chick myoblasts. 337 92

Sudden unexpected death occurs in one quarter of deaths in Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). People with RTT show a variety of autonomic nervous system (ANS) abnormalities and mouse models show similar problems including QTc interval prolongation and hypothermia. To explore the role of cardiac problems in sudden death in RTT, we characterized cardiac rhythm in mice lacking Mecp2 function. Male and female mutant mice exhibited spontaneous cardiac rhythm abnormalities including bradycardic events, sinus pauses, atrioventricular block, premature ventricular contractions, non-sustained ventricular arrhythmias, and increased heart rate variability. Death was associated with spontaneous cardiac arrhythmias and complete conduction block. Atropine treatment reduced cardiac arrhythmias in mutant mice, implicating overactive parasympathetic tone. To explore the role of MeCP2 within the parasympathetic neurons, we selectively removed MeCP2 function from cholinergic neurons (MeCP2 ChAT KO), which recapitulated the cardiac rhythm abnormalities, hypothermia, and early death seen in RTT male mice. Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotypes. Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.
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PMID:Methyl-CpG binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis. 2815 85