Format

Send to:

Choose Destination
See comment in PubMed Commons below
Eur J Pharmacol. 2001 Sep 28;428(1):69-79.

Nornicotine, a nicotine metabolite and tobacco alkaloid: desensitization of nicotinic receptor-stimulated dopamine release from rat striatum.

Author information

  • 1College of Pharmacy and Graduate Center for Toxicology, University of Kentucky, Lexington 40536-0082, USA. LDWOSKIN@POP.UKY.EDU

Abstract

Nornicotine, a major tobacco alkaloid and nicotine metabolite, accumulates in rat brain in pharmacologically relevant concentrations following repeated nicotine administration. Nornicotine-evoked striatal dopamine release is Ca2+-dependent, stereoselective and sensitive to nicotinic receptor antagonists, indicating nicotinic receptor-mediation. The present study determined if S-(-)-nornicotine desensitizes nicotinic receptors and if cross-desensitization to S-(-)-nicotine occurs. S-(-)-Nicotine (10 and 100 nM) diminished [3H]overflow from [3H]dopamine-preloaded rat striatal slices following subsequent superfusion with 10 microM S-(-)-nicotine (46% and 74%, respectively) or 10 microM S-(-)-nornicotine (59% and 81%, respectively). S-(-)-Nornicotine (1 and 10 microM) diminished the response to subsequent superfusion with 10 microM S-(-)-nornicotine (85% and 97%, respectively) or 10 microM S-(-)-nicotine (82% and 88%, respectively). Thus, similar to S-(-)-nicotine, S-(-)-nornicotine desensitizes nicotinic receptors. but with approximately 12-fold lower potency. Cross-desensitization suggests involvement of common nicotinic receptor subtypes. Therefore, S-(-)-nicotine metabolites, such as nornicotine, have neuropharmacologically relevant effects.

PMID:
11779039
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk