The m2 muscarinic acetylcholine receptors are coupled to multiple signaling pathways via pertussis toxin-sensitive guanine nucleotide regulatory proteins.
J Pharmacol Exp Ther
; 258(3): 938-44, 1991 Sep.
Article
in En
| MEDLINE
| ID: mdl-1653846
ABSTRACT
The muscarinic m1 and m2 receptors are functionally coupled to multiple effectors via distinct guanine nucleotide regulatory proteins (G-proteins) defined by their pertussis toxin (PTX) sensitivity. Both receptors are coupled to the hydrolysis of phosphoinositides (PI), whereas only the m2 receptors inhibit cAMP formation. This study examines how the selective interactions of these two receptors with G-proteins may govern their specific functional coupling to the two second messenger pathways. Murine fibroblasts (B82) transfected with the rat m1 or m2 receptor genes were used to test the PTX sensitivity of the m1 and m2 receptor-mediated pathways. It was found that the stimulation of PI hydrolysis and inhibition of cyclic AMP mediated by m2 receptors had similar PTX sensitivity (IC50 = 0.14 ng/ml and 0.26 ng/ml), whereas the m1-mediated PI hydrolysis was PTX insensitive. The EC50 value for carbachol in the m1 receptor-mediated PI hydrolysis was 9.5 microM, whereas those for the m2 receptor-mediated PI hydrolysis and inhibition of cyclic AMP formation were 0.3 microM and 1.2 microM, respectively. The potency of carbachol correlated well with its binding affinities for the two receptor subtypes. These results suggest that the m2 receptors are coupled to multiple pathways via PTX-sensitive G-proteins, which are distinct from those that interact with the m1 receptor. The formation of functional receptor-G-protein complexes may be selective and governed by the efficiencies in coupling between receptors and G-proteins.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virulence Factors, Bordetella
/
Signal Transduction
/
Receptors, Muscarinic
/
GTP-Binding Proteins
/
Pertussis Toxin
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
J Pharmacol Exp Ther
Year:
1991
Document type:
Article