Autoradiographic detection of kinin receptors in the human medulla of control, hypertensive, and diabetic donors

Abstract

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, and B2. Functional and binding studies suggested that B1 and B2 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 [125I]HPP-HOE140 (B2 receptor) and [125I]HPP[des-Arg10]-HOE140 (B1 receptor). Data showed specific binding sites for B2 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 B2 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). B2 receptor binding sites were seemingly increased in the same medullary nuclei of two diabetic specimens. Specific binding sites for B1 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 B2 receptors are upregulated in medullary cardiovascular centers of subjects afflicted of cardiovascular diseases.

Chronic Infusion of Amyloid-β Peptide and Sustained Attention Altered α7 Nicotinic Receptor Density in the Rat Brain

“…The method used was based on a previously described procedure [31]. Serial sections of brains (20 m) were cut on a cryostat chamber (-20°C to -22°C, Microm HM 505 N, Francheville, France), thaw-mounted on gelatin-coated slides, desiccated for 5 min at room temperature and kept at -80°C until use.…”

Targeting Kinin Receptors for the Treatment of Neurological Diseases

“…In the rat and human spinal dorsal horn, in spite of the immunohistochemical detection of B 1 receptors [93,95], B 1 receptor binding sites are almost undetectable [72,113,114]. This discrepancy between binding and immunohistochemical studies may be due to the lower sensitivity of the former approach.…”

“…The enzymes, the substrates and the receptors of the kallikrein-kinin system have all been identified in different areas of the human [72][73][74] and rat [63,[75][76][77] central nervous system. In particular, tissue kallikrein has been found at high concentrations in the hypothalamus, pituitary and pineal gland, but also in the cortex, brainstem and cerebellum, while kininases are diffuse in all brain areas [78,79].…”

“…BK-like immunoreactivity has been localized in rat and guinea-pig spinal cord neurons [18,80] and in neuronal cells of the rat hypothalamus, periaqueductal gray matter, perirhinal and cingulate cortices, the ventral portion of caudate-putamen, and the lateral septal area [81]. B 2 receptors are widely distributed in mammalian brain [63,72,75,77,82], while in the rat spinal cord they have been identified in the dorsal horn and in particular on the terminals of Aδ and C sensory fibers and of bulbospinal noradrenergic fibers [2,83]. Thus, it has been suggested that, through B 2 receptor activation, kinins exert a role of CNS neuromediator, being involved in the control of nociception and blood pressure [18].…”

“…In mice, an higher level of B 1 receptor basal expression may contribute to spinal nociceptive processing and pain behavior in response to thermal and chemical noxious stimuli [103]. In man, however, a functional role for the central B 1 receptor in acute pain is unlikely, based on its low basal expression [72]. Hence, evidence from various animal models (with the exception of mice) pleads in favor of the general concept that the B 1 receptor is involved only in persistent and chronic inflammatory pain [2,71].…”