Presynaptic and Postsynaptic Effects of Neuropeptide Y in the Rat Pineal Gland

: Neuropeptide Y is colocalized with noradrena‐line in sympathetic fibers innervating the rat pineal gland. In this article we present a study of the effects and mechanisms of action of neuropeptide Y on the pineal noradrenergic transmission, the main input leading to the rhythmic secretion of melatonin. At the presynaptic level, neuropeptide Y inhibits by 45%, with an EC50 of 50 nM, the potassium‐evoked noradrenaline release from pineal nerve endings. This neuropeptide Y inhibition occurs via the activation of pertussis toxin‐sensitive G protein‐coupled neuropeptide Y‐Y2 receptors and is independent from, but additive to, the α2‐adrenergic inhibition of noradrenaline release. At the postsynaptic level, neuropeptide Y decreases by a maximum of 35%, with an EC50 of 5 nM, the β‐adrenergic induction of cyclic AMP elevation via the activation of neuropeptide Y‐Y1 receptors. This moderate neuropeptide Y‐induced inhibition of cyclic AMP accumulation, however, has no effect on the melatonin secretion induced by a β‐adrenergic stimulation. On the contrary, in the presence of 1 mM ascorbic acid, neuropeptide Y potentiates (up to threefold) the melatonin secretion. In conclusion, this study has demonstrated that neuropeptide Y modulates the noradrenergic transmission in the rat pineal gland at both presynaptic and postsynaptic levels, using different receptor subtypes and transduction pathways.