title: Modulation of neuropeptide Y expression in rat brain neuronal cultures.
abstract: Neuropeptide Y (NPY) and its encoding mRNA were measured in neurons co-cultured from rat basal forebrain and cerebral cortex. NPY was synthesized and released in a manner consistent with secretion-synthesis coupling; depolarization increased each in a calcium-dependent manner. The accumulation of NPY encoding mRNA was elevated by a muscarinic receptor blocker, without changes in transmitter release or peptide synthesis, thereby consistent with a membrane potential-independent mechanism. Changes in intrinsic muscarinic transmission could nonetheless be expressed rapidly as an elevation in NPY levels by depolarizing the neurons subsequent to muscarinic receptor blockade. This depolarization-induced elevation of NPY subsequent to muscarinic receptor blockade was dependent on the presence of extracellular calcium ions. Forskolin and pertussis toxin also increased NPY encoding mRNA levels in a manner that was not additive with muscarinic receptor blockade. These results suggest that one or more muscarinic receptors may tonically modulate NPY synthesis via changes in adenylate cyclase activity, providing a model for the non-homeostatic modulation of neuropeptide turnover.
authors.affiliation: Department of Clinical Affairs, Amgen Inc., Thousand Oakes, CA 91320.
authors.forename: J J
authors.initials: JJ
authors.lastname: Poulakos
authors.forename: W J
authors.initials: WJ
authors.lastname: Millard
authors.forename: E M
authors.initials: EM
authors.lastname: Meyer
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000096:biosynthesis*; D051381:Rats; D013569:Synapses / Q000502:physiology*
chemical_list: D009478:Neuropeptide Y; D001285:Atropine; D000109:Acetylcholine