Autoradiographic distribution and alterations of kinin B 2 receptors in the brain and spinal cord of streptozotocin‐diabetic rats

This study investigates whether bradykinin (BK) B 2 receptor binding sites are increased in the brain and thoracic spinal cord of streptozotocin (STZ)‐diabetic rats at 2, 7, and 21 days posttreatment by in vitro autoradiography with the radioligand [ 125 I]HPP‐Hoe 140. In control and diabetic rats, specific binding sites for B 2 receptors were detected in the brain and in various laminae of the spinal cord, predominantly in superficial laminae ( K d = 34 pM). In diabetic rats, B 2 receptor densities were significantly increased in lamina l of the dorsal horn (+35% at 7 and 21 days), spinal trigeminal nucleus (+70% at 7 and 21 days) and nucleus tractus solitarius (+100% at 2 and 7 days). B 2 receptor analogues D‐Arg[Hyp 3 ,Thi 5 ,D‐Tic 7 ,Oic 8 ]‐BK (Hoe 140), 3‐(4 hydroxyphenyl)propionyl‐Hoe 140 (HPP‐Hoe 140), LF16‐0687 mesylate ((2‐Pyrrolidinecarboxamide, N‐[3‐[[4‐aminoiminomethyl)benzoyl]amino]propyl]‐1‐[[2,4‐dichoro‐3‐[[(2,4‐dimethyl‐8‐quinolinyl)oxy]methyl]phenyl]sulfonyl]‐(2S)‐(9Cl)), and BK decreased binding of [ 125 I]‐HPP‐Hoe 140 in the spinal dorsal horn, with K i values of 0.5, 1.5, 3.2, and 3.7 nM, respectively. These values were not significantly different in diabetic rats at 7 days (0.5 (Hoe 140), 0.7 (HPP‐Hoe 140), 1.2 (BK), and 1.7 (LF16‐0687) nM). While des‐Arg 10 ‐Hoe 140 was three orders of magnitude less potent than Hoe 140, B 1 receptor agonist (des‐Arg 9 ‐BK) and antagonist (AcLys[D‐βNal 7 ,Ile 8 ]des‐Arg 9 ‐BK, R‐715) did not affect [ 125 I]‐HPP‐Hoe 140 binding at 1 μM concentration. Data suggest a very discrete and temporal increase of B 2 receptor density (without affinity changes) in the spinal cord and hindbrain of STZ‐diabetic rats. This contrasts with the early induction and over‐expression of B 1 receptors reported in the brain and spinal cord of STZ‐diabetic rats. Synapse 58:184–192, 2005. © 2005 Wiley‐Liss, Inc.