Neuropeptide Y modulation of A1 noradrenergic neuron input to supraoptic vasopressin cells

A1 noradrenaline (NA) neurons provide a direct excitatory input to supraoptic nucleus (SON) vasopressin (VP) cells. Many A1 cells contain neuropeptide Y (NPY) and past studies have established that NPY exerts excitatory postsynaptic effects on VP cell activity. We have now investigated whether NPY might also modulate A1 input to VP cells via presynaptic mechanisms. Experiments done in pentobarbitone-anesthetized rats demonstrated that SON application of NPY (10 microM) excited VP cells but also depressed their response to activation of the A1 input. These two effects were not correlated, suggesting independent mechanisms. The putative Y1 agonist [Leu31,Pro34]NPY (10 microM) also excited VP cells but did not alter their response to activation of the A1 input. In contrast, the putative Y2 receptor agonist Ac-[Leu28,Leu31]NPY24-36 mimicked the synaptic depression produced by NPY but did not significantly alter spontaneous activity. These data are consistent with the proposal that NPY acts on Y1-like receptors to excite VP cells but can also act on a presynaptic Y2-like receptor to depress A1-VP cell synaptic transmission.