Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y₂ receptor

Abstract

1 The action of analogues and C-terminal fragments of neuropeptide Y (NPY) was examined on excitatory synaptic transmission in area CAl of the rat hippocampal slice in vitro, by use of intracellular and extracellular recordings, to determine by agonist profile the NPY receptor subtype mediating presynaptic inhibition. 2 Neither NPY, analogues nor fragments of NPY affected the passive or active properties of the postsynaptic CAL pyramidal neurones, indicating their action is at a presynaptic site. 3 The full-sequence analogues, peptide YY (PYY) and human NPY (hNPY), were equipotent with NPY at the presynaptic receptor, while desamido hNPY was without activity. 4 NPY2-36 was equipotent with NPY. Fragments as short as NPY13-36 were active, but gradually lost activity with decreasing length. NPY16-36 had no effect on extracellular field potentials, but still significantly inhibited excitatory postsynaptic potential amplitudes. Fragments shorter than NPY16-36 had no measurable effect on synaptic transmission. 5 The presynaptic NPY receptor in hippocampal CAL therefore shares an identical agonist profile with the presynaptic Y2 receptor at the peripheral sympathetic neuroeffector junction.

Modified, cyclic dodecapeptide analog of neuropeptide Y is the smallest full agonist at the human Y2 receptor

“…In the initial studies characterizing NPY receptor subtypes [4], the Y2 receptor was distinguished from the Y1 receptor by the fact that the former can recognize C-terminal segments of the hormone. Further investigations showed that activity is maintained in the C-terminal moiety, such as NPY(16~36) [25]. These results led us to speculate that a modified segment of NPY Ac-25 36 could be sufficient for Y2 receptor recognition.…”

Mechanisms of Neuropeptide Y, Peptide YY, and Pancreatic Polypeptide Inhibition of Identified Green Fluorescent Protein-Expressing GABA Neurons in the Hypothalamic Neuroendocrine Arcuate Nucleus

“…Coapplication of Y 1 and Y 2 antagonists completely eliminated NPY-evoked hyperpolarization, suggesting a role for postsynaptic Y 2 receptors. In some regions of the brain, such as the hippocampus, Y 2 receptors are primarily involved in presynaptic inhibition with little postsynaptic effect (Colmers et al, 1991;McQuiston and Colmers, 1996). In contrast, ARC GABA neurons showed a direct robust hyperpolarizing response to Y 2 agonists.…”

An intracellular study of pretectal influence on the optic tectum of the frog, Rana catesbeiana

“…Previous immunocytochemical studies [21] have revealed that the pretectal Lpd/P nuclei contain neuropeptide Y (NPY)-like immunoreactivity cells whose fibers distribute in the superficial layers of the ipsilateral tectum (except lamina A), where they partially overlap retinal recipient laminae [22,23] . Because it is known that NPY can reduce the excitatory input, as observed in the rat hippocampus [24] , it is likely that the inhibitory inputs from pretectal cells are attributable to NPY-like immunoreactivity. These neurons may play an inhibitory role in control of visual information flow in the optic tectum of frogs.…”