Hippocampal sympathetic ingrowth and cholinergic denervation uniquely alter muscarinic receptor subtypes in the hippocampus. 1995

L E Harrell, and K Kolasa, and D S Parsons, and V Ayyagari
Department of Neurology, Veterans Administration Medical Center, Birmingham, AL, USA.

Following cholinergic denervation of the hippocampus by medial septal lesions, and unusual neuronal reorganization occurs, in which peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus. Previously, we have found that both hippocampal sympathetic ingrowth (HSI) and cholinergic denervation (CD), alone, altered the total number and affinity of muscarinic cholinergic receptors (mAChR). In this study, we utilized the muscarinic antagonist [3H]Pirenzepine, in combination with membrane radioligand binding techniques, to determine the effects of HSI and CD on hippocampal M1 and M1 + M3 mAChR subtypes, 4 weeks after MS lesions. In both the dorsal and ventral hippocampus, HSI was found to markedly diminish the number of M1 AChRs, while CD was found to increase the number of M1 AChRs. Neither treatment affected the affinity of the M1 AChR. However, when M1 + M3 binding was assessed, CD was found to decrease the affinity in both hippocampal regions, without altering the number of receptors. Neither affinity nor number of M1 + M3 receptors was altered by HSI. The results of this study suggest that both cholinergic denervation and hippocampal sympathetic ingrowth uniquely affect hippocampal muscarinic receptors.

UI MeSH Term Description Entries
D008297 Male Males
D009412 Nerve Fibers Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM. Cerebellar Mossy Fibers,Mossy Fibers, Cerebellar,Cerebellar Mossy Fiber,Mossy Fiber, Cerebellar,Nerve Fiber
D010890 Pirenzepine An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients. Gastrotsepin,Gastrozepin,L-S 519,LS-519,Piren-Basan,Pirenzepin,Pirenzepin Von Ct,Pirenzepin-Ratiopharm,Pirenzepine Dihydrochloride,Pyrenzepine,Ulcoprotect,Ulgescum,Dihydrochloride, Pirenzepine,LS 519,LS519,Piren Basan,Pirenzepin Ratiopharm,Von Ct, Pirenzepin
D011813 Quinuclidinyl Benzilate A high-affinity muscarinic antagonist commonly used as a tool in animal and tissue studies. Benzilate, Quinuclidinyl
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D011976 Receptors, Muscarinic One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D003714 Denervation The resection or removal of the nerve to an organ or part. Laser Neurectomy,Neurectomy,Peripheral Neurectomy,Radiofrequency Neurotomy,Denervations,Laser Neurectomies,Neurectomies,Neurectomies, Laser,Neurectomies, Peripheral,Neurectomy, Laser,Neurectomy, Peripheral,Neurotomies, Radiofrequency,Neurotomy, Radiofrequency,Peripheral Neurectomies,Radiofrequency Neurotomies
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses

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