Presynaptic alpha 2-adrenoceptor antagonism by verapamil but not by diltiazem in rabbit hypothalamic slices.
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 microM) 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 microM had no effect on the electrically evoked release of [3H]-noradrenaline, but increased the basal outflow of radioactivity at 10 and 100 microM. 3 The preferential alpha 2-adrenoceptor antagonist, yohimbine (0.1 microM) significantly antagonized the inhibitory effect of clonidine or adrenaline on [3H]-noradrenaline overflow elicited by electrical stimulation. Verapamil (3 microM) also antagonized this inhibitory effect of the alpha 2-adrenoceptor agonists on [3H]-noradrenaline release. In contrast to these results, exposure to diltiazem (10 microM) was ineffective in blocking the action of the alpha 2-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 alpha 2-adrenoceptor antagonist, diltiazem is devoid of presynaptic alpha 2-adrenoceptor antagonist properties.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D002121:Calcium Channel Blockers; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D014700:Verapamil; D004110:Diltiazem; D003042:Cocaine; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine