CHANGES OF NEUROPEPTIDE-Y MESSENGER-RNA AND PEPTIDE BY DRUGS INFLUENCING ENDOGENOUS NOREPINEPHRINE CONTENT IN CEREBROCORTEX OF THE RAT

Cotransmission of classic transmitters at the synapse has been mention ed for both the CNS and the PNS. Neuropeptide Y (NPY) is a cotransmitt er in noradrenergic neurotransmission, In an attempt to understand the heteroregulation of norepinephrine (NE) and NPY biosynthesis, the pre sent study was performed using radioimmunoassay of NPY and northern bl otting of cDNA probes for characterization of NPY mRNA, Values of NPY- like immunoreactivity (NPY-ir) were elevated in the cerebrocortex from rats that received treatment with fusaric acid, an inhibitor of dopam ine-beta-hydroxylase, with a parallel decrease in NE, Similar results were also observed in rats treated with DSP-4, an alkylator of vesicle s in noradrenergic nerve terminals, Moreover, cerebrocortical NPY-ir w as reduced in rats receiving treatment with pargyline, an inhibitor of monoamine oxidase, with an elevation of catecholamine in parallel. Ac tivity of NPY mRNA was modified by these drugs in a similar way, Howev er, values of NPY-ir and NE in the cerebrocortex were not influenced b y treatment with sodium nitroprusside or guanethidine at a dose produc ing hypotensive effect. Mediation of hypotensive reflex can thus be ru led out, The data obtained suggest that in vivo decrease of NE by drug s increases biosynthesis of NPY in the cerebrocortex of rats.