Faculty Collaboration Database

[3H]tetraphenylphosphonium accumulation in cerebral cortical synaptosomes as a measure of nicotine-induced changes in membrane potential. J Pharmacol Exp Ther 1991 Dec;259(3):1118-23

Date

12/01/1991

Pubmed ID

1762066

Scopus ID

2-s2.0-0026357502 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

The effect of nicotine on synaptosomal membrane potential in P2 preparations of rat cerebral cortex was investigated using a membrane permeant, lipophilic cation, [3H]tetraphenylphosphonium ([3H]TPP+). [3H]TPP+ accumulated in synaptosomes in a time-dependent manner and its accumulation was decreased when the extracellular potassium concentration was increased and in the presence of the sodium channel toxin, veratridine. Nicotine (1-1000 microM) decreased the accumulation of [3H]TPP+ in both P2 synaptosomal preparations and in synaptosomes purified using Percoll gradients. This effect of nicotine was mimicked by other nicotinic agonists (1,1-dimethyl-4-phenylpiperazinium iodide, cytisine, suberyldicholine and acetylcholine) and was partially blocked by 10 microM mecamylamine and 30 microM hexamethonium. Atropine (1 microM) and the removal of calcium from the incubation mixture both enhanced the effect of nicotine while the addition of physostigmine (10 microM) reduced the nicotine-induced decrease in [3H]TPP+ accumulation, evidence that acetylcholine released from the synaptosomes by nicotine may produce hyperpolarization of synaptosomes via stimulation of presynaptic muscarinic receptors. It is concluded that the effect of nicotine on [3H]TPP+ accumulation is mediated by nicotine stimulation of a ganglionic-type nicotinic cholinergic receptor and that this method of determining synaptosomal membrane potential will provide a functional measure of presynaptic nicotinic receptor activation.

Author List

Hillard CJ, Pounds JJ

Author

Cecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Atropine
Cerebral Cortex
Ganglionic Stimulants
Male
Membrane Potentials
Nicotine
Onium Compounds
Organophosphorus Compounds
Rats
Rats, Inbred Strains
Receptors, Nicotinic
Synaptosomes
Tritium