Cholinergic ligand-induced affinity changes in Torpedo californica acetylcholine receptor

The binding of cholinergic ligands to Torpedo californica acetylcholine receptor has been studied in vitro by inhibition of the time course of 125I-labeled α-bungarotoxin-receptor complex formation. The extent of inhibition was dependent on the duration of exposure to the ligand, the apparent affinity for ligand increasing with time, and was reversible upon removal of ligand. Ligand concentration, temperature, and Ca2+ ions influenced this effect which is reminiscent of receptor desensitization in vivo. Such effects were observed both for a cholinergic agonist, carbamylcholine, and for an antagonist, bis(3-aminopyridinium)-1,10-decane diiodide. A minimal model is discussed which can account for these effects and for receptor ligand association leading to postsynaptic depolarization

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