Neuropeptide Y potentiates norepinephrine-stimulated inositol phosphate production in the rat tail artery.

We have recently demonstrated the ability of neuropeptide Y to augment norepinephrine-stimulated contractions of the rat tail artery. In [3H]myo-inositol labeled segments of rat tail artery, addition of a concentration of neuropeptide Y (10(-8) M) known to potentiate contractile responses produced no effect on the basal accumulation of [3H]inositol phosphates. Addition of norepinephrine (10(-7) M), however, resulted in the rapid accumulation of [3H]inositol 1,4,5-trisphosphate to 325 +/- 29% of basal levels within 5 min. This effect of norepinephrine on [3H]inositol 1,4,5-trisphosphate accumulation was mirrored by significant increases (274 +/- 25% of control) in total [3H]inositol phosphates. When neuropeptide Y and norepinephrine were added together, the norepinephrine-stimulated increase in [3H]inositol 1,4,5-trisphosphate was significantly augmented (467 +/- 35% of control) as was the increase measured in total [3H]inositol phosphates (366 +/- 21% of control). We suggest that the ability of neuropeptide Y to augment norepinephrine-induced contraction of the rat tail artery is due, at least in part, to the ability of neuropeptide Y to increase norepinephrine-stimulated phospholipase C activity in vascular smooth muscle and may represent the mechanism of action of this co-neurotransmitter in vivo.