Functional modulation of human "ganglionic-like" neuronal nicotinic acetylcholine receptors (nAChRs) by L-type calcium channel antagonists

Biochem Biophys Res Commun. 1995 Aug 15;213(2):657-62. doi: 10.1006/bbrc.1995.2182.

Abstract

Recent studies suggest that the neuronal nicotinic acetylcholine receptors present on chromaffin cells contain a 1,4-dihydropyridine-sensitive site whose occupation blocks membrane depolarization (1). In the present study, several L-type Ca2+ channel blockers inhibited the activation of the nAChRs present in the human neuroblastoma cell line, IMR 32, in a dose-dependent manner with IC50 values ranging from 0.8-3 microM. In contrast, omega-Conotoxin GVIA and omega-Agatoxin IVA had no effect up to 100 microM. Furthermore, the inorganic channel blocker, cadmium, had no effect either alone or on the modulatory role of the L-type antagonists, suggesting that the effects of these agents on nAChRs are not mediated via an interaction with calcium channels but possibly via a direct interaction with the nAChR ionophore.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Cadmium / pharmacology
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / physiology*
  • Diltiazem / pharmacology
  • Humans
  • Isradipine / pharmacology
  • Neuroblastoma
  • Neurons / physiology*
  • Nicotine / pharmacology
  • Nifedipine / pharmacology
  • Nimodipine / pharmacology
  • Peptides / pharmacology
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / physiology*
  • Spider Venoms / pharmacology
  • Tumor Cells, Cultured
  • Verapamil / pharmacology
  • omega-Agatoxin IVA
  • omega-Conotoxin GVIA

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Peptides
  • Receptors, Nicotinic
  • Spider Venoms
  • omega-Agatoxin IVA
  • Cadmium
  • Nimodipine
  • Nicotine
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • omega-Conotoxin GVIA
  • Verapamil
  • Diltiazem
  • Nifedipine
  • Isradipine