Islet-activating protein (pertussis toxin) diminishes alpha 2-adrenoceptor mediated effects on noradrenaline release

The effect of islet-activating protein (IAP) on alpha 2-adrenoceptor mediated modulation of noradrenaline release in the rabbit hippocampus was studied. Slices of the hippocampus were incubated for 6 h with IAP, subsequently loaded with 3H-noradrenaline and superfused continuously. IAP-pretreatment significantly enhanced the electrically evoked transmitter release and diminished the facilitatory effect of the alpha 2-adrenoceptor antagonist yohimbine. In addition, the inhibitory effect of the alpha 2-adrenoceptor agonist clonidine was reduced. These results provide circumstantial evidence that an inhibitory guanine-nucleotide-binding protein, most probably Ni of a presynaptically located adenylate cyclase, is involved in the alpha 2-autoreceptor mediated modulation of noradrenaline release.