title: Age-related changes of the binding of [3h]SA4503 to sigma1 receptors in the rat brain.
abstract: We have recently developed 1-([3-O-methyl-11C]3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine ([11C]SA4503) as a selective radioligand for mapping sigma1 receptors in the brain by positron emission tomography (PET). In the present short communication we evaluated the age-related changes of the binding of this ligand to sigma1 receptors in Fisher-344 rats (1.5-, 6-, 12-, and 24-month-old) by the in vitro binding assay. We also measured the binding of [3H](+)-pentazocine to sigma1 receptors and the binding of [3H]1,3-di-O-tolylguanidine to sigma2 receptors, which are current standard methods. The specific binding of the three radioligands increased age-dependently. Both Kd and Bmax values of the 24-month-old rats for each radioligand were significantly higher than those of the young rats (1.5- and 6-month-old). The increased numbers of both sigma1 and sigma2 receptor subtypes in the aged rats compensate for the lowered affinity, and rather enhanced the radioligand-receptor binding. The results contrast strikingly with the age-dependent decrease in the dopaminergic, cholinergic and glutamatergic receptors that are reported to be correlated with the sigma receptors, and indicate that a PET study with [11C]SA4503 to evaluate the aging process in humans would be of great interest.
authors.affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan. ishiwata@pet.tmig.or.jp
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsuno
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D010423:Pentazocine / Q000493:pharmacokinetics; D010879:Piperazines / Q000493:pharmacokinetics*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D017480:Receptors, sigma / Q000378:metabolism*; D012746:Sexual Abstinence; D000097605:Sigma-1 Receptor
chemical_list: D002250:Carbon Radioisotopes; D006146:Guanidines; D010423:Pentazocine; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor; C101789:SA 4503; C050232:1,3-ditolylguanidine