Homologous mutations near the junction of the sixth transmembrane domain and the third extracellular loop lead to constitutive activity and enhanced agonist affinity at all muscarinic receptor subtypes

Journal of Pharmacology and Experimental Therapeutics

Volumn 300, Issue 3, 2002, Pages 810-817

  Ford, Diane J ^a,b,c   Essex, Anthony ^a,b,c   Spalding, Tracy A ^a,b,c   Burstein, Ethan S ^a,b,c   Ellis, John ^a,b,c,d  

^a Department of Pharmacology ^*  (United States)

^b PENN STATE COLLEGE OF MEDICINE   (United States)

^c ACADIA PHARMACEUTICALS INC   (United States)

^d PENN STATE MILTON S HERSHEY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINE; ATROPINE; CARBACHOL; MUSCARINIC RECEPTOR; MUSCARINIC RECEPTOR BLOCKING AGENT; PROLINE; RECEPTOR SUBTYPE; SERINE; TYROSINE;

AGONIST; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMAL CELL; ARTICLE; CELL JUNCTION; CONTROLLED STUDY; DRUG RECEPTOR BINDING; GENETIC TRANSFECTION; INDUCED MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; RECEPTOR AFFINITY;

3T3 CELLS; ACETYLCHOLINE; ALGORITHMS; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMALS; CELL MEMBRANE; EXTRACELLULAR SPACE; MICE; MOLECULAR SEQUENCE DATA; MUSCARINIC AGONISTS; MUTAGENESIS; MUTATION; RECEPTORS, MUSCARINIC;

EID: 0036175129     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.300.3.810     Document Type: Article

References (41)

1. Functional role in ligand binding and receptor activation of an asparagine residue present in the sixth transmembrane domain of all muscarinic acetylcholine receptors
2. Identification of a family of muscarinic acetylcholine receptor genes
3. Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes
4. 12: Transduction of proliferative signals
5. International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors
6. Constitutive receptor systems for drug discovery
7. Use of constitutive G protein-coupled receptor activity for drug discovery
8. 50) of an enzymatic reaction
9. Mutagenesis of residues adjacent to transmembrane prolines alters D1 dopamine receptor binding and signal transduction
10. Pharmacological properties of 5-hydroxytryptamine(4) receptor antagonists on constitutively active wild-type and mutated receptors
11. Stimulation of arachidonic acid release and inhibition of mitogenesis by cloned genes for muscarinic receptor subtypes stably expressed in A9 L cells
12. Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function
13. G-protein-independent signaling by G-protein-coupled receptors
14. Activating and inactivating mutations in N- and C-terminal i3 loop junctions of muscarinic acetylcholine Hm1 receptors
15. Pharmacological characterization of human ml muscarinic acetylcholine receptors with double mutations at the junction of TM VI and the third extracellular domain
16. Differential modulation of agonist potency and receptor coupling by mutations of Ser388Tyr and Thr389Pro at the junction of transmembrane domain VI and the third extracellular loop of human M(1) muscarinic acetylcholine receptors
17. Cloned muscarinic receptor subtypes expressed in A9 L cells differ in their coupling to electrical responses
18. The classification of seven transmembrane receptors in recombinant expression systems
19. Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation
20. Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281→isoleucine) in the extracellular domain of the thyrotropin receptor
21. Characterization of heterogeneous mutations causing constitutive activation of the luteinizing hormone receptor in familial male precocious puberty
22. Primary structure of porcine cardiac muscarinic acetylcholine receptor deduced from the cDNA sequence
23. Familial male precocious puberty
24. Molecular cloning and expression of a fifth muscarinic acetylcholine receptor
25. A simple assay for DNA transfection by incubation of the cells in culture dishes with substrates for β-galactosidase
26. Protein measurement with the Folin phenol reagent
27. 1 muscarinic acetylcholine receptor revealed by scanning mutagenesis
28. 2-adrenergic receptors based upon characteristics in primary structure
29. 2+ cascades
30. Review: Amino acid domains involved in constitutive activation of G-protein-coupled receptors
31. Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes
32. Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors
33. Constitutively active mutants of the alpha 2-adrenergic receptor
34. A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model
35. A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia
36. How receptor mutagenesis may confirm or confuse receptor classification
37. Pharmacology of a constitutively active muscarinic receptor generated by random mutagenesis
38. Identification of a ligand-dependent switch within a muscarinic receptor
39. Constitutive activation of the m5 muscarinic receptor by a series of mutations at the extracellular end of transmembrane 6
40. Characterisation of a cloned human 5-HT1A receptor cell line using [35S] GTP gamma S binding
41. In Chinese hamster ovary K1 cells dog and human thyrotropin receptors activate both the cyclic AMP and the phosphatidylinositol 4,5-bisphosphate cascades in the presence of thyrotropin and the cyclic AMP cascade in its absence