Characterization and presynaptic modulation of stimulation-evoked exocytotic co-release of noradrenaline and neuropeptide Y in guinea pig heart.

The relationship between noradrenaline and neuropeptide Y (NPY) release was investigated in the in situ perfused guinea pig heart with intact sympathetic innervation. For determination of NPY concentrations in the perfusate, a specific radioimmunoassay was employed and further characterized. Electrical stimulation of the left stellate ganglion (4, 8, 12, and 50 Hz; for 10 min) evoked a calcium-dependent and frequency-related overflow of noradrenaline and NPY, which was positively correlated (r = 0.83; p less than 0.001; n = 25). When two subsequent stimulations (12 Hz; each for 1 min) were performed in the same heart, addition of noradrenaline (10 microM) 5 min prior to the second stimulation reduced NPY overflow by 43 +/- 10%. The stimulated release of noradrenaline and NPY was increased by the alpha 2-adrenoceptor antagonist yohimbine (1 microM) to 170 +/- 10% and 199 +/- 26%, and attenuated by the alpha 2-adrenoceptor agonist B-HT 920 (1 microM) to 70 +/- 9% and 68 +/- 9%, respectively. The adenosine analogue cyclohexyladenosine (1 microM) significantly reduced the stimulated overflow of both noradrenaline (to 57 +/- 5%) and NPY (to 73 +/- 8%). Exogenous NPY (100 nM) attenuated the stimulated overflow of noradrenaline by 30 +/- 6%. Uptake1 blockade with desipramine (100 nM) or nisoxetine (100 nM) prior to the second stimulation significantly increased noradrenaline overflow and attenuated that of NPY; the attenuation of the stimulation-evoked overflow of NPY was abolished by yohimbine (1 microM). Our results indicate that electrical stimulation induces a calcium-dependent, exocytotic co-release of noradrenaline and NPY.(ABSTRACT TRUNCATED AT 250 WORDS)