INSULIN RECEPTOR-RELATED RECEPTOR MESSENGER-RIBONUCLEIC-ACID IS FOCALLY EXPRESSED IN SYMPATHETIC AND SENSORY NEURONS AND RENAL DISTAL TUBULE CELLS

The insulin receptor-related receptor (IRR) demonstrates striking stru ctural homology to the insulin receptor (IR) and insulin-like growth f actor-I receptor (IGFR), suggesting that IRR is a member of the IR fam ily. However, the endogenous ligand and biological role for this ''orp han'' receptor are unknown. To identify potential sites of action for the IRR, in situ hybridization was employed to reveal cellular pattern s of IRR gene expression in the developing and adult rat and in the ad ult human kidney. From embryonic days 15-20, IRR mRNA is most abundant in sensory neurons of the trigeminal and dorsal root ganglia and, to a lesser extent, neurons of the autonomic system. IRR gene expression diminishes in the majority of sensory neurons postnatally, but remains abundant in a subpopulation of adult rat trigeminal and dorsal root g anglion neurons. IRR mRNA is localized in peripheral autonomic ganglia localized in the adrenal medulla and renal hilum in the adult. From b irth to maturity, IRR mRNA is abundant in renal epithelial cells focal ly localized in the distal tubule in both rat and human kidney. The sp ecificity of this pattern of IRR gene expression was demonstrated by h ybridization of serial tissue sections with two different nonoverlappi ng cRNA probes. Nonspecific signal, as measured by IRR sense probe hyb ridization, was negligible. This highly restricted pattern of IRR gene expression is in marked contrast to the very widespread pattern of ge ne expression demonstrated by the IR and IGFR. This study showed that IRR, IR, and IGFR mRNAs were colocalized in some sensory neurons, sugg esting the possibility for hybrid receptor formation in these cells. I n summary, IRR gene expression is focally localized in sensory and aut onomic neurons and renal distal tubule cells. These observations sugge st that the IRR, in contrast to the related IR and IGFR, serves a narr ow cell-specific role.