Autoradiographic detection of kinin receptors in the human medulla of control, hypertensive, and diabetic donors
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2002-04-01
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Artigo
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Kinins have been elected to the status of central neuromediators. Their effects are mediated through the activation of two G-protein-coupled receptors, denoted B-1 and B-2. Functional and binding studies suggested that B-1 and B-2 receptors are upregulated in the medulla and spinal cord of hypertensive and diabetic rats. the aim of this study was to localize and quantify kinin receptors in post-mortem human medulla obtained from normotensive, hypertensive, and diabetic subjects, using in vitro receptor autoradiography with the radioligands [I-125]HPP-HOE140 (B-2 receptor) and [I-125]HPP[des-Arg(10)]-HOE140 (B-1 receptor). Data showed specific binding sites for B-2 receptor (0.4-1.5 fmol/mg tissue) in 11 medullary nuclei from 4 control specimens (paratrigeminal > ambiguus > cuneate, gelatinous layer of the caudal spinal trigeminal nucleus > caudal and interpolar spinal trigeminal, external cuneate, solitary tract > hypoglossal > gracile > inferior olivary nuclei). Increased density of B-2 receptor binding sites was observed in seven medullary nuclei of four hypertensive specimens (paratrigeminal > external cuneate > interpolar and caudal spinal trigeminal, gracile, inferior olivary > hypoglossal nuclei). B-2 receptor binding sites were seemingly increased in the same medullary nuclei of two diabetic specimens. Specific binding sites for B-1 receptor (1.05 and 1.36 fmol/mg tissue) were seen only in the inferior olivary nucleus in two out of the ten studied specimens. the present results support a putative role for kinins in the regulation of autonomic, nociceptive, and motor functions at the level of the human medulla. Evidence is also provided that B-2 receptors are upregulated in medullary cardiovascular centers of subjects afflicted of cardiovascular diseases.
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Canadian Journal of Physiology and Pharmacology. Ottawa: Natl Research Council Canada, v. 80, n. 4, p. 249-257, 2002.