Lesion of septal-hippocampal neurons with 192 IgG-saporin alters function of M1 muscarinic receptors

Autor: C. Gaughan, Y. Assouline, P.E. Potter
Rok vydání: 1999
Předmět:
Male
medicine.medical_specialty
Cholinergic Agents
In Vitro Techniques
Muscarinic Agonists
Biology
Hippocampus
Muscarinic agonist
Choline O-Acetyltransferase
Rats
Sprague-Dawley
Norepinephrine
Cellular and Molecular Neuroscience
GTP-Binding Proteins
Parasympathetic Nervous System
Internal medicine
Muscarinic acetylcholine receptor
medicine
Muscarinic acetylcholine receptor M4
Oxotremorine
Animals
Autonomic Pathways
N-Glycosyl Hydrolases
Neurons
Pharmacology
Guanylyl Imidodiphosphate
Immunotoxins
Receptor
Muscarinic M1
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
Antibodies
Monoclonal
Muscarinic acetylcholine receptor M3
Muscarinic acetylcholine receptor M2
Muscarinic acetylcholine receptor M1
Receptors
Muscarinic
Saporins
Pirenzepine
Electric Stimulation
Rats
Endocrinology
Ribosome Inactivating Proteins
Type 1
Septum Pellucidum
medicine.drug
Zdroj: Neuropharmacology. 38:579-586
ISSN: 0028-3908
Popis: Cholinergic neurons projecting from the medial septum to the hippocampus were lesioned with the selective neurotoxin 192 IgG-saporin. Injection of 300 ng of 192 IgG-saporin into the medial septum produced a 60% decrease in choline acetyltransferase activity. M1 muscarinic receptor function was examined by measuring enhancement of evoked release of norepinephrine from rat hippocampal slices by the M1 selective agonist McN-A-343. In hippocampal slices from rats which were lesioned with 192-saporin, the response to McN-A-343 was reduced compared to sham-operated controls. Pirenzepine binding demonstrated no change in M1 receptor number or affinity. However, the curve for displacement of pirenzepine by the muscarinic agonist oxotremorine-M was shifted to the right in hippocampal tissue from lesioned rats. This shift was identical to that produced by addition of the non-hydrolyzable GTP analogue GppNHp, which uncouples the M1 muscarinic receptor/G-protein complex. These results suggest that lesion of septal-hippocampal cholinergic inputs causes uncoupling of the M1 muscarinic receptor, decreasing responsiveness to stimulation. These findings are similar to reports of decreased M1 muscarinic receptor coupling to G-proteins and loss of function in Alzheimer’s disease. The 192 IgG-saporin lesion may provide a viable animal model in which to study uncoupling of G-proteins and M1 muscarinic receptors.
Databáze: OpenAIRE
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