MODULATION OF NEUROPEPTIDE-Y EXPRESSION IN RAT-BRAIN NEURONAL CULTURES

Neuropeptide Y (NPY) and its encoding mRNA were measured in neurons co -cultured from rat basal forebrain and cerebral cortex. NPY was synthe sized and released in a manner consistent with secretion-synthesis cou pling; depolarization increased each in a calcium-dependent manner. Th e accumulation of NPY encoding mRNA was elevated by a muscarinic recep tor blocker, without changes in transmitter release or peptide synthes is, thereby consistent with a membrane potential-independent mechanism . Changes in intrinsic muscarinic transmission could nonetheless be ex pressed rapidly as an elevation in NPY levels by depolarizing the neur ons subsequent to muscarinic receptor blockade. This depolarization-in duced 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 t hat was not additive with muscarinic receptor blockade. These results suggest that one or more muscarinic receptors may tonically modulate N PY synthesis via changes in adenylate cyclase activity, providing a mo del for the non-homeostatic modulation of neuropeptide turnover.