QUANTITATION, CELLULAR-LOCALIZATION AND REGULATION OF NEUROKININ RECEPTOR GENE-EXPRESSION WITHIN THE RAT SUBSTANTIA-NIGRA

The diverse biological effects of substance P and related peptides are mediated by multiple neurokinin receptors. The CNS sites of neurokini n receptor biosynthesis have not been fully elucidated and little is k nown about the regulation of neurokinin receptor gene expression. In t he present study, the abundance of neurokinin-1, neurokinin-2 and neur okinin-3 receptor messenger RNAs in various rat brain regions was quan titated using a sensitive solution hybridization assay. Midbrain neuro kinin receptor gene expression was then examined in derail. In situ hy bridization experiments localized high levels of neurokinin-3 receptor messenger RNA to presumptive dopamine neurons, as evidenced by sensit ivity to 6-hydroxydopamine lesions and the presence of tyrosine hydrox ylase messenger RNA in serial sections. Lesions of nigral afferent (in cluding substance P-containing) pathways from the caudate-putamen incr eased both nigral neurokinin-3 and neurokinin-1 receptor messenger RNA levels two- to three-fold. These data provide the anatomical substrat e for physiological data suggesting that substance P (released from st riatonigral neurons) may act on nigral cells through neurokinin-1 rece ptors, while the substance P co-transmitter neurokinin A may act prefe rentially on dopamine neurons through neurokinin-3 receptors. The magn itude of denervation-induced changes in neurokinin receptor messenger RNAs suggests significant plasticity of neurokinin receptor gene expre ssion.