Association of functional alteration in intracellular signal transduction systems with the occurrence of up-regulation of muscarinic receptors in primary cultured neurons.
1. Alterations in intracellular biosignaling systems associated with the up-regulated muscarinic receptor were investigated using primary cultured neurons exposured to 10 nM atropine for 5 days. 2. In neurons treated with atropine, the response of PI turnover to muscarinic stimulation decreased in comparison with that in non-treated neurons. 3. The GTP gamma S-stimulated PI turnover also reduced in neurons possessing up-regulated muscarinic receptor, although phospholipase C activity was not different in these two types of neurons. 4. In addition, the long-term exposure (5 days) to atropine induced the increase in GTPase activity and [3H]GppNHp binding. 5. These results suggest that the decreased response of PI turnover to muscarinic stimulation may be attributed to the functional deterioration of G-protein itself and/or coupling between G-protein and phospholipase C. 6. The present results also strongly suggest that the accentuation of the function of G protein may occur in association with the up-regulation of muscarinic receptor.
Ohkuma
S
S
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Kishi
M
M
Ma
F H
FH
Kuriyama
K
K
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000502:physiology; D011247:Pregnancy; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D009419:Nerve Tissue Proteins; D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins