Muscarinic cholinergic receptor-mediated phosphoinositide metabolism in peripheral nerve
| Autor: | Liliana N. Berti-Mattera, Joseph Eichberg, Nancy S. Day |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Atropine
Male medicine.medical_specialty Inositol Phosphates Biology Pertussis toxin Phosphatidylinositols Biochemistry Cellular and Molecular Neuroscience chemistry.chemical_compound GTP-Binding Proteins Internal medicine Muscarinic acetylcholine receptor medicine Animals Inositol Virulence Factors Bordetella Myelin Sheath Adenosine Diphosphate Ribose Hydrolysis Osmolar Concentration Muscarinic acetylcholine receptor M3 Inositol trisphosphate Rats Inbred Strains Pirenzepine Receptors Muscarinic Sciatic Nerve Rats Endocrinology medicine.anatomical_structure chemistry Pertussis Toxin Peripheral nervous system Carbachol medicine.drug |
| Zdroj: | Journal of neurochemistry. 56(6) |
| ISSN: | 0022-3042 |
| Popis: | Few receptor-mediated phenomena have been detected in peripheral nerve. In this study, the ability of the muscarinic cholinergic receptor agonist carbamylcholine to enhance phosphoinositide (PPI) breakdown in sciatic nerve was investigated by measuring the accumulation of inositol phosphates. Rat sciatic nerve segments were prelabeled with myo-[3H]inositol and then incubated either with or without carbamylcholine in the presence of Li+. [3H]Inositol monophosphate ([3H]IP) accumulation contained most of the radioactivity in inositol phosphates, with [3H]inositol bisphosphate ([3H]IP2) and [3H]inositol trisphosphate ([3H]IP3) accounting for 7-8% and 1-2% of the total, respectively. In the presence of 100 microM carbamylcholine, [3H]IP accumulation increased by up to 150% after 60 min. The 50% effective concentration for the response was determined to be 20 microM carbamylcholine and stimulated IP generation was abolished by 1 microM atropine. Enhanced accumulation of IP2 and IP3 was also observed. Determination of the pA2 values for the muscarinic receptor antagonists atropine (8.9), pirenzepine (6.5), AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one) (5.7), and 4-diphenylacetoxy-N-methylpiperidinemethiodide (4-DAMP) (8.6) strongly suggested that the M3 muscarinic receptor subtype was predominantly involved in mediating enhanced PPI degradation. Following treatment of nerve homogenates and myelin-rich fractions with pertussis toxin and [32P]NAD+, the presence of an ADP-ribosylated approximately 40-kDa protein could be demonstrated. The results indicate that peripheral nerve contains key elements of the molecular machinery needed for muscarinic receptor-mediated signal transduction via the phosphoinositide cycle. |
| Databáze: | OpenAIRE |
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