NEUROPEPTIDE-Y AND GALANIN BINDING-SITES IN RAT AND MONKEY LUMBAR DORSAL-ROOT GANGLIA AND SPINAL-CORD AND EFFECT OF PERIPHERAL AXOTOMY

Using monoiodinated peptide YY (PYY) and galanin as radioligands, and neuropeptide Y (NPY) fragments, the distribution of NPY binding sites and its subtypes Y1 and Y2, and of galanin binding sites, was investig ated in rat and monkey lumbar (L) 4 and L5 dorsal root ganglia (DRG) a nd spinal cord before and after a unilateral sciatic nerve cut, ligati on or crush. Receptor autoradiography revealed that [I-125]PYY bound t o some DRG neurons and a few nerve fibres in normal rat DRG, and most of these neurons were small. NPY binding sites were observed in lamina e I-IV and X of the rat dorsal horn and in the lateral spinal nucleus, with the highest density in laminae I-II. [I-125]PYY binding was most strongly attenuated by NPY13-36, a Y2 agonist, and partially inhibite d by [Leu(31),Pro(34)]NPY, a Y1 agonist, in both rat DRG and the dorsa l horn of the spinal cord. These findings suggest that Y2 receptors ar e the main NPY receptors in rat DRG and dorsal horn, but also that Y1 receptors exist. After sciatic nerve cut, PYY binding markedly increas ed in nerve fibres and neurons in DRG, especially in large neuron prof iles, and in laminae III-IV of the dorsal horn, as well as in nerve fi bres in dorsal roots and the sciatic nerve. Incubation with NPY13-36 c ompletely abolished PYY binding, which was also reduced by [Leu(31),Pr o(34)] NPY. However, the increase in PYY binding seen in laminae I-IV of the ipsilateral dorsal horn after axotomy was not observed after co incubation with [Leu(31),Pro(34)] NPY. NPY binding sites were seen in a few neurons in monkey DRG and in laminae I-II, X and IX of the monke y spinal cord. The intensity of PYY binding in laminae I-II of the dor sal horn was decreased after axotomy. Galanin receptor binding sites w ere not observed in rat DRG, but were observed in the superficial dors al horn of the spinal cord, mainly in laminae I-II. Axotomy had no eff ect on galanin binding in rat DRG and dorsal horn. However, galanin re ceptor binding was observed in many neurons in monkey L4 and L5 DRG an d in laminae I-IV and X of monkey L4 and L5 spinal cord, with the high est intensity in laminae I-II. No marked effect of axotomy was observe d on the distribution and intensity of galanin binding in monkey DRG o r spinal cord. The present results indicate that after axotomy the syn thesis of NPY receptors is increased in rat DRG neurons, especially in large neurons, and is transported to the laminae I-IV of the ipsilate ral dorsal horn and into the sciatic nerve. No such up-regulation of t he NPY receptor occurred in monkey DRG after axotomy. The Y2 receptor seems to be the main NPY receptor in DRG and the dorsal horn of the ra t and monkey spinal cord, but Y1 receptors also exist. The increase in NPY binding sites in laminae I-IV of the dorsal horn after axotomy pa rtly represents Y1 receptors. In contrast to the rat, galanin binding sites could be identified in monkey lumbar DRG. No effect of axotomy o n the distribution of galanin binding sites in rat or monkey DRG and d orsal horn was detected, suggesting their presence on local dorsal hor n neurons (or central afferents).