Changes in ³H-Quinuclidinyl Benzilate Binding and Protein Synthesis in the Striatum Following Chronic Administrations of Muscarinic Agonist

Abstract

Injection of the muscarinic agonist oxotremorine into rat striatum for seven consecutive days resulted in a 44% in ³H-quinuclidinyl benzilate (³H-QNB) binding, and it caused decreases in binding affinity to agonists. Furthermore, it eliminated the shift from the high affinity site to the low affinity site that occurs in the presence of 5''-guanylyl imidodiphosphate (Gpp (NH)p). In addition, oxotremorine caused a 1.5-fold increase in the incorporation of ³H-leucine into the striatum, suggesting that it increased the syntheses of proteins other than the muscarinic receptor protein. The present results show that chronic treatment of the striatum with oxotremorine causes alterations in not only the quantity, but also the sensitivity of muscarinic receptors to guanine nucleotide.