Molecular Mechanism Underlying the Occurrence of Supersensitivity at Muscarinic Receptors: Analysis Using Cerebral Cortical Neurons in Primary Culture
Chronic treatment with muscarinic antagonists is known to induce an up-regulation at muscarinic receptors in various organs (Takeyasu et al., 1979; Barak et al., 1981; Hedlund, 1986; Goodbar andBartifai, 1988). There is, however, no actual information on the alteration in intracellular biosignaling systems associated with muscarinic receptors under these conditions. Recently, Goodbar and Bartfai (1988) have reported that the increase of muscarinic receptor induced by a long-term administration of a muscarinic antagonist, atropine, leads to a decrease in the responsiveness of phosphoinositide (PI) hydrolysis to carbachol stimulation, although the mechanism of the reduction in carbachol stimulated PI turnover in the brain with up-regulated muscarinic receptor is not demonstrated. In this study, we have, therefore, attempted to clarify the mechanism underlying such a reduction of PI turnover in response to muscarinic stimulation using mouse cerebral cortical neurons in primary culture, which possess metabolic and functional activity as cholinergic neurons (Ohkuma et al., 1987).
KeywordsPrimary Culture Muscarinic Receptor Inositol Phosphate GTPase Activity Muscarinic Antagonist
Unable to display preview. Download preview PDF.
- Goodbar, L. and Bartifai, T., Long-term atropine treatment lower the efficacy of carbachol to stimulate phosphatidylinositol breakdown in the cerebral cortex and hippocampus of rats, Biochem. J. 250:727–734 (1988).Google Scholar
- Ohkuma, S., Ma, F.-H., Tomono, S., Kishi, M. and Kuriyama, K., Development of cerebral cholinergic neurons in primary culture, Japan. J. Pharmacol. 43(Suppl.):148p (1987).Google Scholar