Interaction between neuropeptide Y and noradrenaline on central catecholamine neurons

Abstract

DESPITE their widespread occurrence in the central nervous system, interactions between co-localized transmitters and their receptors remain poorly understood. Noradrenergic neurons of the nucleus locus coeruleus contain the peptide co-transmitter neuropeptide Y (refs 1,2). In locus coeruleus cells, stimulation of α₂-adrenoceptors^3,4 or opioid μ-receptors^5,6 increases a potassium conductance and thereby leads to hyperpolarization and inhibition of spontaneous firing. Coupling between these receptors and the inward rectifying K⁺ channels involves a pertussis toxin-sensitive GTP-binding protein (G_i or G_o)⁷. Here we investigate whether the neuropeptide Y and α₂-receptors of locus coeruleus neurons interact with one another. When administered alone, neuropeptide Y reduces the discharge of action potentials, probably by increasing the permeability of the membrane to potassium ions through the activation of a G protein ; this effect is reduced in the presence of α₂-adrenoceptor antagonists. Moreover, the peptide selectively increases the hyperpolarizing effect of α₂-agonists, but does not enhance responses to opioid μ-agonists. We suggest that noradrenaline and its co-transmitter neuropeptide Y stimulate separate receptors, which influence each other in a specific way.