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Novel 1,4‐Dihydropyridine (Bay K 8644) Facilitates Calcium‐Dependent [ 3 H]Noradrenaline Release from PC 12 Cells
Author(s) -
Albus Udo,
Habermann Ernst,
Ferry David R.,
Glossmann Hartmut
Publication year - 1984
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1984.tb12729.x
Subject(s) - nitrendipine , dihydropyridine , calcium , membrane channel , calcium channel , chemistry , agonist , voltage dependent calcium channel , biophysics , endocrinology , biochemistry , biology , receptor , organic chemistry
The effects of the novel 1,4‐dihydropyridine Bay K 8644 [methyl‐1,4‐dihydro‐2,6‐dimethyl‐3‐nitro‐4‐(2‐trifluoromethylphenyl)‐pyridine‐5‐carboxylate] on the release of [ 3 H]noradrenaline in cultured PC 12 cells were investigated. K + in a concentration‐dependent manner evoked 3 H‐transmitter release with an EC 50 of 50‐56 mM. Bay K 8644 at 30 nM potentiated the K + ‐evoked [ 3 H]noradrenaline release; however, in the absence of calcium neither K + evoked nor Bay K 8644 enhanced [ 3 H]noradrenaline release. At a K + concentration of 25 mM, Bay K 8644 stimulated [ 3 H]noradrenaline release fivefold, with an EC 50 of 10 nM, and 100 nM of the calcium channel blocker nitrendipine shifted the concentration response curve of Bay K 8644 to the right in an apparently competitive fashion. Nitrendipine blocked the Bay K 8644‐potentiated release with an EC 50 of 700 nM in the presence of 500 nM Bay K 8644. [ 3 H]Nitrendipine bound to a saturable population of binding sites on PC 12 cell membranes with a B max of 180 fmol μmg ‐1 of membrane protein and a K D of 0.9 nM. Bay K 8644 inhibited [ 3 H]nitrendipine binding with a K 1 of 16 nM. It is concluded that Bay K 8644 binds to, and stabilizes, the open state of calcium channels and thus acts as a “calcium agonist” to mediate calcium‐dependent cellular events such as catecholamine release from PC 12 cells.