Cellular and Molecular Neurobiology

, Volume 17, Issue 1, pp 35–50

Potency of Agonists and Competitive Antagonists on Adult- and Fetal-Type Nicotinic Acetylcholine Receptors

  • C. Spencer Yost
  • Bruce D. Winegar
Article

DOI: 10.1023/A:1026325020191

Cite this article as:
Yost, C.S. & Winegar, B.D. Cell Mol Neurobiol (1997) 17: 35. doi:10.1023/A:1026325020191

Abstract

1. The potency of agonists and competitive antagonists on the two expressed forms of the nicotinic acetylcholine receptor (adult or junctional subtype, ε-AChR; fetal or extrajunctional subtype, γ-AChR) have not previously been compared systematically in homogeneous receptor preparations.

2. Each subtype of the receptor was expressed separately in Xenopus oocytes by cytoplasmic injection of combinations of RNA transcribed in vitro. The presence of each type of receptor was confirmed by single-channel recordings. Expressing oocytes were assayed using discontinuous, single-electrode voltage clamp by measuring peak currents in response to test compounds.

3. The extrajunctional subtype was more potently activated by the nicotinic agonist dimethylphenyl piperazinium iodide (DMPP) than was the junctional form. There was no statistically significant difference in potency between the two subtypes for other nicotinic agonists (nicotine, cytisine and succinylcholine). The rank order of potency for ε-AChR was succinylcholine>cytisine>DMPP>nicotine, and that for γ-AChR was DMPP>cytisine>succinylcholine>nicotine.

4. Two agonists (cytisine and succinylcholine) displayed six- to eight-fold greater intrinsic activity in activating ε-AChR over γ-AChR. There was no difference between the two forms of receptor in efficacy for nicotine.

5. The extrajunctional form was much more potently inhibited by the steroidal competitive antagonist pancuronium than was the junctional receptor. However, there was no significant difference in potency of inhibition by the curariform drug atracurium.

6. Contrary to previous reports, there is no consistent relation between the effect of agonists and antagonists and the subtype of receptor. These data suggest that the resistance or sensitivity to these agents seen in various clinical settings are related to other cellular factors.

acetylcholine receptoragonistsnondepolarizing muscle relaxantsextrajunctional receptorneuromuscular junctionvoltage clampoocytes

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • C. Spencer Yost
    • 1
  • Bruce D. Winegar
    • 1
  1. 1.Department of Anesthesia, Medical Sciences 255University of CaliforniaSan Francisco