title: Multiple NPY receptors coexist in pre- and postsynaptic sites: inhibition of GABA release in isolated self-innervating SCN neurons.
abstract: Although NPY has been shown to influence the action of many transmitters in the brain, modulation of GABA, the primary inhibitory transmitter, has not been detected with electrophysiology. Using whole-cell patch-clamp recording, we found that NPY has a large modulatory effect on GABAergic neurons of the suprachiasmatic nucleus (SCN) that act as the circadian clock in the mammalian brain. NPY, acting at both Y1- and Y2-like receptors, reduced the frequency of spontaneous miniature inhibitory postsynaptic currents while having little effect on the postsynaptic GABA receptors, suggesting a presynaptic mechanism of NPY action. In single self-innervating neurons, application of either Y1 or Y2 agonists to the same neuron significantly inhibited the evoked autaptic GABA release. The use of single-neuron microcultures has allowed the demonstration that a single peptide, NPY, has two different receptors coded for by different genes in the same axon terminal. The Y1 and Y2 agonists also inhibited whole-cell calcium currents when applied to the same neuron, indicating a coexistence of Y1- and Y2-like receptors in the postsynaptic cell body. The self-innervating cell model we use here may be applicable generally for discriminating presynaptic versus postsynaptic actions of other neurotransmitters and neuromodulators and locating their subtype receptors.
authors.affiliation: Section of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: A N
authors.initials: AN
authors.lastname: van den Pol
mesh_terms: D000818:Animals; D001464:Barium / Q000037:antagonists & inhibitors / Q000502:physiology; D002469:Cell Separation; D004553:Electric Conductivity; D018756:GABA Antagonists / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018756:GABA Antagonists; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D001464:Barium; D005680:gamma-Aminobutyric Acid