한국응용약물학회:학술대회논문집 (Proceedings of the Korean Society of Applied Pharmacology)
- 한국응용약물학회 1996년도 춘계학술대회
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- Pages.206-206
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- 1996
Mutation of a Transposed Amino Acid Triplet Repeat Enhances Coupling of m1 Muscarinic Receptor to Activation of Phospholipase C
- Lee, Seok-Yong (Department of Pharmacology, Catholic University Medical College) ;
- Cho, Tai-Soon (Department of Pharmacology, College of Pharmacy, Sung Kyun Kwan University)
- 발행 : 1996.04.01
초록
The C-terminus ends of the second putative transmembrane domains of both m1 and m2 muscarinic receptors contain a triplet of amino acid residues consisting of leucine (L), tyrosine (Y) and threonine (T), This triplet is repeated as LYT-LYT in m2 receptors at the interface between the second transmembrane domain and the first extracellular loop. Interestingly, however, it is repeated in a transposed fashion (LYT-TYL) in the sequence of m1 receptors. In this work we employed site-directed mutagenesis to investigate the possible significance of this unique sequence diversity for determining the distinct differential drug-receptor interaction and cellular function at m1 muscarinic receptor. Mutation of the LYTTYL sequence of m1 receptors to the corresponding m2 receptor LYTLYT sequence, however, did not result in a significant change in the binding affinity of the agonist carbachol or in the affinity of the majority of a series of receptor antagonists which are able to discriminate between wild-type m1 and m2 receptors. Surprisingly, the LYTLYT ml receptor mutant demonstrated markedly enhanced coupling to activation of phospholipase C without a change in its coupling to increased cyclic AMP formation. There was also an enhanced receptor sensitivity in transducing elevation of intracellular Ca
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