Expression and distribution of kinin B1 receptor in the rat brain and alterations induced by diabetes in the model of streptozotocin.
A role for kinin B1 receptors was suggested in the spinal cord and peripheral organs of streptozotocin (STZ)-diabetic rats. The present study aims at determining whether B1 receptors are also induced and over-expressed in the brain of STZ-rats at 2, 7, and 21 days post-treatment. This was addressed by in situ hybridization using the [35S]-UTPalphaS-labeled riboprobe and by in vitro autoradiography with the radioligand [125I]-HPP-des-Arg10-Hoe 140. In control rats, B1 receptor mRNA was found widely distributed in many brain regions. Low mRNA levels were found in thalamus and hypothalamus (7-12 nCi/g) while high mRNA signals were detected in cortical regions and hippocampus (18-29 nCi/g). In diabetic rats, B1 receptor mRNA was markedly increased in hippocampus, temporal/parietal cortices and amygdala at 2 and 7 days (+88 to +150%). Low densities of B1 receptor binding sites were detected in all analyzed regions in control rats (0.18-0.37 fmol/mg tissue). In diabetic rats, B1 receptor binding sites were significantly increased in hippocampus, amygdala, temporal/parietal, and perhinal/piriform cortices (+ 55 to + 165 %) at 7 days only. Results highlight an early but transient and reversible up-regulation of B1 receptors in specific brain regions of STZ-diabetic rats. This may offer the advantage of reducing putative central side effects with B1 receptor antagonists if used for the treatment of diabetic complications in the periphery.
Campos
Maria Martha
MM
Département de Physiologie, Faculté de Médecine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
Ongali
Brice
B
De Souza Buck
Hudson
H
Schanstra
Joost-Peter
JP
Girolami
Jean-Pierre
JP
Chabot
Jean-Guy
JG
Couture
Réjean
R
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000096:biosynthesis / Q000378:metabolism*
D015347:RNA Probes; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1