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-adrenoceptors3,4 or opioid μ-receptors5,6 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 (Gi 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. © 1990 Nature Publishing Group.