INFLUENCE OF ACETYLCHOLINE ON BINDING OF 4-[I-125]IODODEXETIMIDE TO MUSCARINIC BRAIN RECEPTORS

The distribution of nicotinic and muscarinic cholinergic receptors in the human brain in vivo has been successfully characterized using radi olabeled tracers and emission tomography. The effect of acetylcholine release into the synaptic cleft on receptor binding of these tracers h as not yet been investigated. The present study examined the influence of acetylcholine on binding of 4-[I-125]iododexetimide to muscarinic cholinergic receptors of porcine brain synaptosomes in vitro. 4-Iodexe timide is a subtype-unspecific muscarinic receptor antagonist with hig h affinity, Acetylcholine competed with 4-[I-125]iododexetimide in a d ose-dependent manner. A concentration of 500 mu M acetylcholine inhibi ted 50% of total specific 4-[I-125]iododexetimide binding to synaptoso mes when both substances were given simultaneously. An 800 mu M acetyl choline solution reduced total specific 4-[I-125]iododexetimide bindin g by about 35%, when acetylcholine was given 60 min after incubation o f synaptosomes with 4-[I-125]iododexetimide. Variations in the synapti c acetylcholine concentration might influence muscarinic cholinergic r eceptor imaging in vivo using 4-[I-123]iododexetimide. Conversely, 4-[ I-123]iododexetimide might be an appropriate molecule to investigate a lterations of acetylcholine release into the synaptic cleft in vivo us ing single photon emission computed tomography. NUCL MED BIOL 25;8:777 -780, 1998. (C) 1998 Elsevier Science Inc..