Regional distribution of Y-receptor subtype mRNAs in rat brain

Molecular cloning techniques have recently led to the identification of a g rowing number of neuropeptide Y-receptor subtypes, suggesting possible subt ype-specific involvement in different physiological processes. Here we repo rt the first study which determines and compares the mRNA expression of all four cloned functional Y-receptor subtypes (Y-1, Y-2, Y-4 and Y-5) in cons ecutive sections of the rat brain on a cellular level, using a uniform in s itu hybridization technique. Our results demonstrate that Y-receptor subtyp e mRNA expression is widely distributed throughout the rat brain. Interesti ngly, coexpression of all four Y-receptors, at different levels, is particu larly evident within the limbic system, including the hypothalamus, hippoca mpus, amygdala, piriform and cingulate cortices and tegmental areas, all of which are heavily involved in behaviour, emotion and homeostatic regulatio n. Particularly interesting is the demonstration that Y-5-receptor mRNA exp ression always coincides with the presence of Y-1-receptor mRNA (although n ot vice versa), possibly due to the overlapping organization and transcript ional control of their genes. However, it is also clear that several brain nuclei display preferential expression of one or a selective combination of Y-receptor subtype mRNAs. Furthermore, it is evident that there is regiona lization of expression within certain loci which express all four receptor subtype mRNAs, particularly within the paraventricular and arcuate hypothal amic nuclei. Our results suggest that some of neuropeptide Y's (NPY) effect s may be mediated through one particular subtype, whereas other physiologic al processes might require the coordinated action of different subtypes wit hin the same or discrete areas.