Presynaptic A2-adrenoceptors and neuropeptide Y Y2 receptors inhibit [3H]noradrenaline release from rat hypothalamic synaptosomes via different mechanisms

Abstract Presynaptic receptors may reduce transmitter release with different mechanisms. Both the α 2 -agonist, clonidine and the Y 2 -agonist, neuropeptide Y fragment 13–36 (NPY 13–36), induce a concentration-dependent inhibition of the 4-aminopyridine (4-AP)-evoked [ 3 H]noradrenaline ([ 3 H]NA) release from hypothalamic synaptosomes. Changes in α 2 - and Y 2 -modulation of noradrenaline (NA) release were observed by lowering the calcium influx with the use of ω-conotoxin (ω-CgTx), a calcium-channel blocking agent. In these experimental conditions, clonidine was less active, whereas NPY 13–36 preserved its efficacy. It therefore seems possible that presynaptic α 2 -adrenoceptors can primarily inhibit NA release by reducing calcium influx via voltage-sensitive calcium channels (VSCC), while Y 2 -receptors may inhibit the intracellular release process with a mechanism independent of the calcium entry.