An M2 muscarinic receptor subtype coupled to both adenylyl cyclase and phosphoinositide turnover.
To investigate whether a particular receptor subtype can be coupled to multiple effector systems, recombinant M2 muscarinic receptors were expressed in cells lacking endogenous receptor. The muscarinic agonist carbachol both inhibited adenylyl cyclase and stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was significantly less efficient and more dependent on receptor levels than the inhibition of adenylyl cyclase. Both responses were mediated by guanine nucleotide binding proteins, as evidenced by their inhibition by pertussis toxin; the more efficiently coupled adenylyl cyclase response was significantly more sensitive. Thus, individual subtypes of a given receptor are capable of regulating multiple effector pathways.
Ashkenazi
A
A
Department of Developmental Biology, Genentech, Inc., South San Francisco, CA 94080.
Winslow
J W
JW
Peralta
E G
EG
Peterson
G L
GL
Schimerlik
M I
MI
Capon
D J
DJ
Ramachandran
J
J
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011994:Recombinant Proteins; D013873:Thionucleotides / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010095:Oxotremorine; D006160:Guanosine Triphosphate; D002217:Carbachol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases