Biomaterial Database

Sidedness and chemical and kinetic properties of the vesamicol receptor of cholinergic synaptic vesicles. 1988

W D Kornreich, and S M Parsons

Department of Chemistry, University of California, Santa Barbara 93106.

Cholinergic synaptic vesicles isolated from Torpedo electric organ contain a receptor for the compound l-2-(4-phenylpiperidino)cyclohexanol (vesamicol, formerly AH5183), which when occupied blocks storage of acetylcholine (AcCh). The inside or outside orientation of the receptor and its chemical and ligand binding kinetics characteristics were studied. Binding of [3H]vesamicol to the receptor is inhibited efficiently by the protein modification reagents 4-(chloromercuri)benzenesulfonate and N,N'-dicyclo-hexylcarbodiimide and by protease treatment of cholate-solubilized receptor. The receptor in native vesicles is resistant to irreversible inactivation by proteases, elevated temperature, or pH extremes. [3H]Vesamicol binding depends on deprotonation of a group of pKa1 = 6.26 +/- 0.03 and protonation of a group of pKa2 = 10.60 +/- 0.04, which is probably the tertiary amine of the drug molecule itself. The membrane-impermeant zwitterionic vesamicol analogue dl-trans-4-oxo-4-[5,6,7,8-tetrahydro-6-hydroxy-7-(4-phenyl-1-piperidinyl )-1- naphthalenyl]amino]butanoic acid (TPNB) is an effective inhibitor of AcCh active transport with an IC50 value of (51 +/- 8) x 10(-9) M. At 23 degrees C, [3H]vesamicol bound to the receptor at a rate of (1.74 +/- 0.06) x 10(5) M-1 s-1, and excess unlabeled vesamicol displaced a low concentration of bound [3H]vesamicol at 0.29 +/- 0.01 min-1. At 0 degrees C, 10 microM unlabeled vesamicol displaced 36 +/- 2% of a low concentration of bound [3H]vesamicol at 0.16 +/- 0.02 min-1 and 64 +/- 2% at 0.013 +/- 0.001 min-1. One micromolar unlabeled vesamicol behaved similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010622	Phencyclidine	A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.	1-(1-Phenylcyclohexyl)piperidine,Angel Dust,CL-395,GP-121,Phencyclidine Hydrobromide,Phencyclidine Hydrochloride,Sernyl,Serylan,CL 395,CL395,Dust, Angel,GP 121,GP121
D010880	Piperidines	A family of hexahydropyridines.
D002799	Cholinergic Fibers	Nerve fibers liberating acetylcholine at the synapse after an impulse.	Cholinergic Fiber,Fiber, Cholinergic,Fibers, Cholinergic
D004557	Electric Organ	In about 250 species of electric fishes, modified muscle fibers forming disklike multinucleate plates arranged in stacks like batteries in series and embedded in a gelatinous matrix. A large torpedo ray may have half a million plates. Muscles in different parts of the body may be modified, i.e., the trunk and tail in the electric eel, the hyobranchial apparatus in the electric ray, and extrinsic eye muscles in the stargazers. Powerful electric organs emit pulses in brief bursts several times a second. They serve to stun prey and ward off predators. A large torpedo ray can produce of shock of more than 200 volts, capable of stunning a human. (Storer et al., General Zoology, 6th ed, p672)	Electric Organs,Organ, Electric,Organs, Electric
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000109	Acetylcholine	A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.	2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000465	Algorithms	A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.	Algorithm
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013572	Synaptic Vesicles	Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.	Synaptic Vesicle,Vesicle, Synaptic,Vesicles, Synaptic