Presynaptic α2‐adrenoceptor antagonism by verapamil but not by diltiazem in rabbit hypothalamic slices

Abstract

1 Rabbit hypothalamic slices prelabelled with [³H]-noradrenaline and superfused with Krebs solution were stimulated electrically at a frequency of 5 Hz. Exposure to verapamil (0.1 to 10 μm) significantly increased, in a concentration-dependent manner, the electrically-evoked overflow of tritium, without affecting the spontaneous outflow of radioactivity. 2 Exposure to diltiazem in concentrations up to 100 μm had no effect on the electrically evoked release of [³H]-noradrenaline, but increased the basal outflow of radioactivity at 10 and 100 μm. 3 The preferential α₂-adrenoceptor antagonist, yohimbine (0.1 μm) significantly antagonized the inhibitory effect of clonidine or adrenaline on [³H]-noradrenaline overflow elicited by electrical stimulation. Verapamil (3 μm) also antagonized this inhibitory effect of the α₂-adrenoceptor agonists on [³H]-noradrenaline release. In contrast to these results, exposure to diltiazem (10 μm) was ineffective in blocking the action of the α₂-adrenoceptor agonist. 4 These results suggest that the two Ca²⁺-antagonists verapamil and diltiazem differ in their ability to affect central noradrenergic neurotransmission. While verapamil is a relatively potent α₂-adrenoceptor antagonist, diltiazem is devoid of presynaptic α₂-adrenoceptor antagonist properties.