| First Author | Guieu R | Year | 2006 |
| Journal | Behav Brain Res | Volume | 166 |
| Issue | 2 | Pages | 230-5 |
| PubMed ID | 16154213 | Mgi Jnum | J:104027 |
| Mgi Id | MGI:3611033 | Doi | 10.1016/j.bbr.2005.08.003 |
| Citation | Guieu R, et al. (2006) CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity. Behav Brain Res 166(2):230-235 |
| abstractText | BACKGROUND: CD26 is a multifunctional cell surface glycoprotein expressed by T and B cells. It exhibits a dipeptidyl-peptidase activity (DPP-IV) that cleaves the penultimate proline from the N-terminus of polypeptides, thereby regulating their activity and concentration. METHODS: Using CD26-/- mice resulting from targeted inactivation of the gene, we examined the consequences of a DPP-IV defect on behavioural response to nociceptive stimuli and concentration of the pain modulator peptides substance P (SP) and endomorphin 2, two DPP-IV substrates. RESULTS: CD26 inactivation induced a three-fold decrease in circulating endopeptidase activity while that found in brain extracts was normal, albeit very weak. CD26-/- mice had high SP concentrations in plasma (3.4+/-1pg/ml versus 1.5+/-0.3pg/ml, P<10(-3)) but not in brain extracts (35+/-12pg/ml versus 32+/-9pg/ml, P>0.05). Endomorphin-2 levels in the two groups were in the same range for plasma and brain extracts. CD26-/- mice displayed short latencies to nociceptive stimuli (hot plate test: 6.6+/-1.2s versus 8.6+/-1.5s, P<10(-4); tail pinch test: 3.1+/-0.6s versus 4.2+/-0.8s, P<10(-3)). Administration of an SP (NK1) receptor antagonist or DPP-IV to CD26-/- mice normalised latencies. DPP-IV inhibitors decreased latencies only in CD26+/+ mice. CONCLUSIONS: Our observations represent the first fundamental evidence showing that DPP-IV influences pain perception via modulation of the peripheral SP concentration. Our work also highlights the role of peripheral NK1 receptors in nociception. |
