Sustained nicotine exposure differentially affects alpha 3 beta 2 and alpha 4 beta 2 neuronal nicotinic receptors expressed in Xenopus oocytes

J Neurochem. 1996 Feb;66(2):667-75. doi: 10.1046/j.1471-4159.1996.66020667.x.

Abstract

To determine whether prolonged exposure to nicotine differentially affects alpha 3 beta 2 versus alpha 4 beta 2 nicotinic receptors expressed in Xenopus oocytes, oocytes were coinjected with subunit cRNAs, and peak responses to agonist, evoked by 0.7 or 7 microM nicotine for alpha 4 beta 2 and alpha 3 beta 2 receptors, respectively, were determined before and following incubation for up to 48 h with nanomolar concentrations of nicotine. Agonist responses of alpha 4 beta 2 receptors decreased in a concentration-dependent manner with IC50 values in the 10 nM range following incubation for 24 h and in the 1 nM range following incubation for 48 h. In contrast, responses of alpha 3 beta 2 receptors following incubation for 24-48 h with 1,000 nM nicotine decreased by only 50-60%, and total ablation of responses could not be achieved. Attenuation of responses occurred within the first 5 min of nicotine exposure and was a first-order process for both subtypes; half-lives for inactivation were 4.09 and 2.36 min for alpha 4 beta 2 and alpha 3 beta 2 receptors, respectively. Recovery was also first-order for both subtypes; half-lives for recovery were 21 and 7.5 h for alpha 4 beta 2 and alpha 3 beta 2 receptors, respectively. Thus, the responsiveness of both receptors decreased following sustained exposure to nicotine, but alpha 4 beta 2 receptors recovered much slower. Results may explain the differential effect of sustained nicotine exposure on nicotinic receptor-mediated neurotransmitter release.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Electric Conductivity
  • Evoked Potentials / drug effects
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurotransmitter Agents / metabolism
  • Nicotine / pharmacology*
  • Oocytes / metabolism
  • Osmolar Concentration
  • Rats
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Time Factors
  • Xenopus laevis

Substances

  • Neurotransmitter Agents
  • Receptors, Nicotinic
  • Nicotine