title: Autoradiographic distribution and alterations of kinin B(2) receptors in the brain and spinal cord of streptozotocin-diabetic rats.
abstract: 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-betaNal(7),Ile(8)]des-Arg(9)-BK, R-715) did not affect [(125)I]-HPP-Hoe 140 binding at 1 microM 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.
authors.affiliation: Département de Physiologie, Faculté de Médecine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Maria Martha
authors.initials: MM
authors.lastname: Campos
authors.forename: Brice
authors.initials: B
authors.lastname: Ongali
authors.forename: Gaétan
authors.initials: G
authors.lastname: Thibault
authors.forename: Witold
authors.initials: W
authors.lastname: Neugebauer
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D001345:Autoradiography; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007457:Iodine Radioisotopes; D007705:Kinins / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013610:Tachycardia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D007457:Iodine Radioisotopes; D007705:Kinins; D008024:Ligands; D043782:Receptor, Bradykinin B2