Molecular Mechanism Underlying the Occurrence of Supersensitivity at Muscarinic Receptors: Analysis Using Cerebral Cortical Neurons in Primary Culture

  • Kinya Kuriyama
  • Seitaro Ohkuma
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 287)


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).


Primary Culture Muscarinic Receptor Inositol Phosphate GTPase Activity Muscarinic Antagonist 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Kinya Kuriyama
    • 1
  • Seitaro Ohkuma
    • 1
  1. 1.Department of PharmacologyKyoto Prefectural University of MedicineKamikyo-ku, Kyoto 602Japan

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