MARKED INCREASE IN CHOLECYSTOKININ-B RECEPTOR MESSENGER-RNA LEVELS INRAT DORSAL-ROOT GANGLIA AFTER PERIPHERAL AXOTOMY

It is now well established that the expression of peptides in rat prim ary sensory neurons is dramatically changed in response to peripheral nerve injury. Thus, as first shown by Jessell et al.15 peripheral axot omy causes a decrease in substance P levels in the dorsal horn of the corresponding spinal cord segments, and this is due to down-regulation of peptide synthesis in dorsal root ganglion neurons.22 In contrast, other peptides such as vasoactive intestinal polypeptide and peptide h istidine isoleucine,27 galanin12 and neuropeptide Y32 are all markedly upregulated in the rat L4 and L5 dorsal root ganglia after sciatic ne rve sectioning. The levels of another peptide, cholecystokinin and its messenger RNA are normally very low or undectable in rat primary sens ory neurons,5,20,24,25,26 but after peripheral axotomy approximately 3 0% of the ganglion neurons express cholecystokinin messenger RNA.30 Du ring the last few years a number of peptide receptors have been cloned , and they all belong to the family of G-protein coupled receptors wit h seven membrane spanning segments,21 among them the two cholecystokin in receptors cholecystokinin(A) and cholecystokinin(B).17,23,34 Ghilar di et al.11 have recently described presence of cholecystokinin(B) bin ding sites in rat dorsal root ganglia neurons. In the present study we report that the messenger RNA for the cholecystokinin(B) receptor is present at very low levels in normal dorsal root ganglia of the rat, b ut axotomy causes a very marked increase in the number of sensory neur ons of all sizes expressing cholecystokinin(B) receptor messenger RNA, suggesting an increased sensitivity to cholecystokinin for many prima ry sensory neurons of different modalities after lesion.