Open AccessCharacterization of Benextramine as an Irreversible α‐Adrenergic Blocker and as a Blocker of Potassium‐Activated Calcium Channels
Author(s) -
PLOTEK Yael,
ATLAS Daphne
Publication year - 1983
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1983.tb07497.x
Subject(s) - prazosin , chemistry , endocrinology , medicine , adrenergic receptor , calcium , alpha (finance) , nifedipine , potassium , biophysics , antagonist , receptor , biochemistry , biology , construct validity , nursing , patient satisfaction , organic chemistry
An irreversible α‐adrenergic blocker, benextramine [ N,N′ ‐bis( o ‐methoxybenzylamine‐ n ‐hexyl)‐cysteamine] was used as a probe to study the possible interrelationship between α‐adrenoceptors and the K + ‐activated Ca 2+ ‐channels. Benextramine, a tetraamine disulfide, acts irreversibly both on the α 1 ‐adrenoceptor ( t 1/2 = 3 min) and the α 2 ‐adrenoceptors. These studies were carried out on rat brain synaptosomes, [ 3 H]prazosin and [ 3 H]clonidine binding. Benextramine blocked Ca 2+ influx in rat brain synaptosomes under both depolarizing (75 mM KCl) and normal conditions (5 mM KCl). Its action at the channel is reversible with IC 50 = 10 ± 5 μM of the net Ca 2+ influex. This makes benextramine a most potent Ca 2+ blocker compared to verapamil or nicardipine (IC 50 = 200 μM and 170 μ, respectively). Pretreatment of rat brain slices with benextramine gave a synaptosomal preparation which was devoid of either α 1 ‐adrenergic or α 2 ‐adrenergic binding capacity due to the irreversible binding of benextramine, but with an undistrubed Ca 2+ influx. Thus, these results suggest that the α‐adrenoceptors and the Ca 2+ ‐channels are independent of each other, and that full occupancy of the α‐receptors does not affect the net calcium flux.