1. Agonist-induced down-regulation of m1 muscarinic receptors and reduction of their mRNA level in a transfected cell line
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Wanida S. Pou, Rochelle M. Long, Esam E. El-Fakahany, Shou Zhen Wang, Carlos Forray, and Jingru Hu
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Agonist ,medicine.medical_specialty ,Carbachol ,Receptor down-regulation ,medicine.drug_class ,Northern blot analysis ,Biophysics ,Down-Regulation ,mRNA regulation ,Biology ,Transfection ,Biochemistry ,Muscarinic agonist ,Cell Line ,Structural Biology ,Internal medicine ,Muscarinic acetylcholine receptor ,Genetics ,medicine ,Chinese hamster ovary cell ,Animals ,RNA, Messenger ,Receptor ,Molecular Biology ,Muscarinic receptor ,Cell Biology ,Muscarinic acetylcholine receptor M1 ,Blotting, Northern ,Molecular biology ,Receptors, Muscarinic ,Quinuclidinyl Benzilate ,Rats ,Kinetics ,Endocrinology ,medicine.drug - Abstract
Agonist-induced reduction in both the number of ml muscarinic receptors and the mRNA coding for the receptor protein was investigated in Chinese hamster ovary (CHO) cells which were transfected with the ml muscarinic receptor gene. Receptor concentration was measured by the specific binding of the muscarinic ligand, [3H]quinuclidinyl benzilate ([3H]QNB), and Northern blot hybridization analysis was used to evaluate the levels of receptor mRNA. Incubation of cells with 1 mM of the muscarinic agonist, carbamylcholine (CBC), for 24 h decreased receptor density and mRNA levels in cells by 65% and 73%, respectively. These results indicate that agonist-induced down-regulation of ml muscarinic receptors might be due to, at least in part, a decrease in receptor synthesis resulting from a reduction in the steady-state level of their mRNA.
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