Neuropeptide Y increases the inhibitory effects of clonidine on potassium evoked3H-noradrenaline but not3H-5-hydroxytryptamine release from synaptosomes of the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat

Summary The release of³H-noradrenaline (³H-NA) and of³H-5-hydroxytryptamine (³H-5-HT) evoked by high-K⁺ (15 mM) was studied in synaptosomes isolated from the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat using a superfusion apparatus. Based on concentration-response curves obtained by analyzing the full-time course of the inhibitory effects of clonidine on³H-NA and on³H-5-HT release neuropeptide Y (NPY) (1 nM) was shown to significantly increase the ability of clonidine to inhibit³H-NA release in synaptosomes isolated from the hypothalamus and from the frontoparietal cortex. NPY (1 nM) alone had no effect on K⁺-evoked³H-NA release from these regions. In contrast, NPY (1 nM) did not modulate the inhibitory effects of clonidine on³H-5-HT release in the above mentioned regions. These results indicate that NPY can increase the sensitivity of the 2-autoreceptors belonging to hypothalamic NA and/or to adrenaline nerve terminals and to cortical NA nerve terminals, while the 2-heteroreceptors inhibiting³H-HT release in the same brain regions appear not to be regulated by high affinity NPY receptors. Thus, 2-autoreceptors and 2-heteroreceptors appear to be differentially controlled by high affinity NPY receptors at least with regard to regulation of³H-NA and³H-5-HT release, respectively.