Persistent occultation of the vesamicol receptor.
By binding to a specific receptor, the drug vesamicol [(-)-trans-2-(4-phenylpiperidino)cyclohexanol] noncompetitively inhibits acetylcholine active transport into synaptic vesicles. An analog [(+/-)-trans-5-amino-2-hydroxy-3-(4-phenylpiperidino) tetralin] of vesamicol has been discovered that causes time- (t1/2 = 2.6 min) and temperature-dependent loss of vesamicol binding that is only slowly reversible (t1/2 for recovery = 5.4 h). Assuming a simple two step process of ligand binding followed by a conformational change, an apparent dissociation constant of 4 x 10(-11) M can be calculated. Other analogs of the vesamicol family of drugs also display similar high-affinity binding to the receptor in a manner which resembles the time dependent effects of reserpine binding to chromaffin granules.
Rogers
G A
GA
Department of Chemistry, University of California, Santa Barbara 93106.
Parsons
S M
SM
D000818:Animals; D002021:Buffers; D004557:Electric Organ / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D011094:Polyethyleneimine / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D012110:Reserpine / Q000494:pharmacology; D013237:Stereoisomerism; D013569:Synapses / Q000187:drug effects; D013696:Temperature; D014101:Torpedo
D002021:Buffers; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D012110:Reserpine; D011094:Polyethyleneimine