Calcium channel 'agonist' BAY K 8644 inhibits calcium antagonist binding to brain and PC12 cell membranes

Brain Res. 1984 Jul 9;305(2):365-8. doi: 10.1016/0006-8993(84)90444-x.

Abstract

BAY K 8644, a drug that elicits calcium-dependent muscle contraction, inhibits binding of the voltage-dependent calcium channel antagonist [3H]nitrendipine to brain and PC12 pheochromocytoma cell membranes. This effect is due to high-affinity (Ki = 4.5 nM) competitive inhibition at the binding site for dihydropyridine calcium antagonists. Allosteric sites that mediate calcium channel blockade by non-dihydropyridine calcium antagonists are not similarly affected. Our findings indicate that BAY K 8644 is active at central, as well as peripheral, calcium channels and are compatible with a multi-state model of the voltage-dependent calcium channel in which antagonist drugs promote a closed state of the channel, while BAY K 8644 promotes an open state.

Publication types

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

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Animals
  • Binding, Competitive
  • Brain / drug effects
  • Brain / metabolism*
  • Calcium / metabolism*
  • Cell Line
  • In Vitro Techniques
  • Ion Channels / drug effects*
  • Ion Channels / metabolism
  • Male
  • Nifedipine / analogs & derivatives*
  • Nifedipine / metabolism
  • Nifedipine / pharmacology
  • Nitrendipine
  • Pheochromocytoma / metabolism*
  • Rats
  • Rats, Inbred Strains

Substances

  • Ion Channels
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Nitrendipine
  • Nifedipine
  • Calcium