Presynaptic regulation of co-release of neuropeptide Y and noradrenaline induced by electrical stimulation of the sympathetic nerve in guinea pig heart

In the present study, co-release of noradrenaline and neuropeptide y (NPY) evoked by electrical stimulation of the left stellate ganglion, was investigated in the in situ perfused guinea pig heart with intact sympathetic innervation, a model modified from Legendorff technique. Endogenous noradrenaline was measured by HPLC and endogenous NPY was determined by RIA. Electrical stimulation of the left stellate ganglion (4, 8, 12 and 50 Hz) evoked a calcium-dependent and frequency-related overflow of noradrenaline and NPY. The release of both transmitters was positively correlated (r = 0.83, p less than 0.001). When two subsequent stimulations were performed in the same heart, adding exogenous noradrenaline before the second stimulation reduced NPY overflow on the contrary, and NPY decreased the overflow of noradrenaline. The stimulated release of noradrenaline and NPY was increased by the alpha 2-adrenergic receptor antagonist yohimbine, and attenuated by the alpha 2-adrenergic receptor agonist B-HT 920, respectively. The adenosine analogue cyclohexyladenosine significantly reduced co-release of noradrenaline and NPY. Blocking the uptake of NA with despramine or Nisoxetine significantly increased noradrenaline overflow, however, NPY release was markedly reduced. We concluded that electrical stimulation can induce calcium-dependent co-release of noradrenaline and NPY, and this co-release of both transmitters is modulated by presynaptic alpha 2-adrenoceptors.