Elsevier

Brain Research

Volume 305, Issue 2, 9 July 1984, Pages 365-368
Brain Research

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

https://doi.org/10.1016/0006-8993(84)90444-XGet rights and content

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 = 4.5nM) 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.

Cited by (30)

  • Molecular Basis for Ligand Modulation of a Mammalian Voltage-Gated Ca<sup>2+</sup> Channel

    2019, Cell
    Citation Excerpt :

    The relatively poor resolution of this specific region, compared to the overall high resolution of the pore domain of rCav1.1-B, may suggest a metastable state of these segments in the present structure (Figure S4E). It has been rigorously characterized that DHP agonists occupy the same binding site as antagonists (Greenberg et al., 1984; Hockerman et al., 1997c; Janis et al., 1984; Peterson et al., 1996; Sanguinetti and Kass, 1984) (Table S1). Consistently, nifedipine and Bay K 8644 can be well overlaid with the dihydropyridine ring completely overlapped, and the phenyl ring aligned on the same plane with slight rotation (Figure 3B).

  • BAY-K 8644

    2009, xPharm: The Comprehensive Pharmacology Reference
View all citing articles on Scopus
View full text