Evidence for functional activity of up-regulated nicotine binding sites in rat striatal synaptosomes.
A number of studies have found that the chronic administration of nicotine causes an increase in the density of nicotinic binding sites in the brain, but it is not known whether these additional binding sites are functionally active receptors. In this study, the effects of 1-week administration of the potent nicotinic agonist, (+)-anatoxin-a (96 nmol/day via osmotic minipumps), was assessed on [3H]nicotine binding and [3H]dopamine uptake and release in rat striatal synaptosomes. Chronic (+)-anatoxin-a treatment resulted in a 32% increase in the Bmax of [3H]nicotine binding in anatoxin-treated animals compared to control. There was a 43% increase in the activity of 3 microM nicotine to release [3H]dopamine from synaptosomes of anatoxin-treated animals, but the release induced by 20 mM K+ depolarization was unaffected. There was no effect of chronic (+)-anatoxin-a treatment on the uptake of [3H]dopamine. A strong positive correlation (r = 0.64) was found between the density of [3H]nicotine binding sites and the nicotine-induced stimulation of [3H]dopamine release in individual animals. These results indicate that (+)-anatoxin-a, like nicotine, produces an up-regulation of nicotine binding sites following chronic administration, and that these additional sites are functional receptors capable of mediating the release of dopamine from striatal synaptosomes.
Rowell
P P
PP
Department of Biochemistry, University of Bath, England.
Wonnacott
S
S
D000818:Animals; D001427:Bacterial Toxins; D001665:Binding Sites; D003342:Corpus Striatum / Q000378:metabolism* / Q000648:ultrastructure; D000087522:Cyanobacteria Toxins; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology; D052998:Microcystins; D009538:Nicotine / Q000378:metabolism* / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*; D014326:Tropanes; D015854:Up-Regulation
D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D014326:Tropanes; D009538:Nicotine; C509783:anatoxin a; D011188:Potassium; D004298:Dopamine