TY - JOUR
T1 - Heterogeneity of binding of muscarinic receptor antagonists in rat brain homogenates
AU - Lee, J. H.
AU - El-Fakahany, E. E.
PY - 1985
Y1 - 1985
N2 - The binding properties of (-)-[3H]quinuclidinyl benzilate and [3H]N-methylscopolamine to muscarinic acetylcholine receptors have been investigated in rat brain homogenates. The binding of both antagonists demonstrated high affinity and saturability. Analysis of the binding data resulted in linear Scatchard plots. However, (-)-[3H]quinuclidinyl benzilate showed a significantly higher maximal binding capacity than that of [3H]N-methylscopolamine. Displacement of both ligands with several muscarinic receptor antagonists resulted in competition curves in accordance with the law of mass-action for quinuclidinyl benzilate, atropine and scopolamine. A similar profile was found for the quaternary ammonium analogs of atropine and scopolamine when [3H]N-methylscopolamine was used to label the receptors. However, when these hydrophilic antagonists were used to displace (-)-[3H]quinuclidinyl benzilate binding, they showed interaction with high- and low-affinity binding sites. On the other hand, the nonclassical muscarinic receptor antagonist, pirenzepine, was able to displace both ligands from two binding sites. The present data are discussed in terms of the relationship of this anomalous heterogenity of binding of these hydrophilic muscarinic receptor antagonists and the proposed M1 and M2 receptor subtypes.
AB - The binding properties of (-)-[3H]quinuclidinyl benzilate and [3H]N-methylscopolamine to muscarinic acetylcholine receptors have been investigated in rat brain homogenates. The binding of both antagonists demonstrated high affinity and saturability. Analysis of the binding data resulted in linear Scatchard plots. However, (-)-[3H]quinuclidinyl benzilate showed a significantly higher maximal binding capacity than that of [3H]N-methylscopolamine. Displacement of both ligands with several muscarinic receptor antagonists resulted in competition curves in accordance with the law of mass-action for quinuclidinyl benzilate, atropine and scopolamine. A similar profile was found for the quaternary ammonium analogs of atropine and scopolamine when [3H]N-methylscopolamine was used to label the receptors. However, when these hydrophilic antagonists were used to displace (-)-[3H]quinuclidinyl benzilate binding, they showed interaction with high- and low-affinity binding sites. On the other hand, the nonclassical muscarinic receptor antagonist, pirenzepine, was able to displace both ligands from two binding sites. The present data are discussed in terms of the relationship of this anomalous heterogenity of binding of these hydrophilic muscarinic receptor antagonists and the proposed M1 and M2 receptor subtypes.
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M3 - Article
C2 - 3839264
AN - SCOPUS:0022259367
SN - 0022-3565
VL - 233
SP - 707
EP - 714
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -