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Multiple NPY Receptors Inhibit GABA_A Synaptic Responses of Rat Medial Parvocellular Effector Neurons in the Hypothalamic Paraventricular Nucleus

Department of Pharmacology (N.P., W.F.C.), University of Alberta, Edmonton, Alberta, Canada T6G 2H7; and Institute of Biochemistry (A.G.B.-S.), University of Leipzig, Leipzig D-04103, Germany

Address all correspondence and requests for reprints to: Dr. William F. Colmers, Department of Pharmacology, University of Alberta, 9-36 Medical Sciences Building, Edmonton, Alberta, Canada T6G 2H7. E-mail: william.colmers{at}ualberta.ca

We have recently shown that NPY and -melanocyte-stimulating hormone, which potently induce or inhibit feeding, respectively, have opposing modulatory actions on GABAergic synapses in the medial parvocellular region of the paraventricular hypothalamic nucleus (mpPVN). Because this action might underlie the effects of NPY on feeding, we have examined the pharmacology of NPY responses using electrophysiological recordings.

Focal electrical stimulation within the PVN elicited a GABA_A synaptic response in some mpPVN neurons, which was reversibly inhibited by NPY in a concentration-dependent manner (EC₅₀ = 28 nM). NPY did not alter the response to the GABA_A agonist, muscimol.

Agonist responses to NPY analogs were not consistent with a single NPY receptor subtype; the most subtype selective agonists were less effective than the more broadly selective ones. Antagonist blockade of individual receptor subtypes partly inhibited NPY action, while fully blocking effects of selective agonists. Combining Y₁ and Y₅ antagonists blocked actions of NPY entirely, but the Y₂ antagonist also completely blocked actions of NPY in some neurons.

NPY inhibits GABA_A synaptic transmission onto mpPVN neurons, but this can be mediated by three different NPY receptors. Controversy regarding the receptor or receptor subtypes involved in NPY-mediated feeding may arise from the multiple NPY receptors present.

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