An 11C-labeled selective adenosine A2A antagonist, (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-[11C]-methylxanthine ([11C]KF17837), was prepared by reaction of (E)-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine and [11C]methyl iodide with decay-corrected radiochemical yield of 19-50%, radiochemical purity of > 99%, sp. act. of 17-100 GBq/mumol and preparation time of 20-25 min. In mice, the myocardium showed the highest (13.4% ID/g) at 5 min after i.v. injection, which decreased gradually with time. The specific myocardial uptake was visualized by gamma-camera. In the brain region the radioactivity level was higher in the A2A receptors-rich striatum than in the cortex and cerebellum. The specific striatal uptake in rats was clearly demonstrated by PET. These results have shown that [11C]KF17837 is a potential PET radioligand for mapping the adenosine A2A receptors in the heart and brain.

Animals↗

PubMedDate not supplied

Neuroreceptor bindings and synaptic activity in visual system of monocularly enucleated rat.

PURPOSE: To study the changes in the distribution of postsynaptic benzodiazepine (BDZ) and presynaptic adenosine A(1) (AA(1)) receptors in the superior colliculus (SC) and visual cortex (VC) of rats following monocular enucleation. METHODS: The right eyes of 6-week-old Long-Evans rats were enucleated and ex vivo autoradiography was performed on the SC and VC obtained at different times up to 8 weeks after the enucleation. [14C]deoxyglucose was used to detect glucose metabolism, and [11C]flumazenil and [1-methyl-(11)C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine ([11C]MPDX) were used to map BDZ and AA(1) receptors, respectively. The receptor-specific binding for 11C was determined, and 11C and 14C activities were evaluated separately in the same tissue by a double tracing method. RESULTS: The uptake of [14C]deoxyglucose in the SC was depressed immediately after enucleation and gradually recovered. The binding of [11C]flumazenil to BDZ receptors in the contralateral SC was increased at week 2, and then returned to the pre-enucleation levels. The uptake of [11C]MPDX by the AA(1) receptors in the contralateral SC decreased by about 67% on day 5 after enucleation and remained low thereafter. In the contralateral VC, the uptake of [14C]deoxyglucose decreased immediately after the enucleation followed by a gradual recovery, whereas the uptake of [11C]flumazenil and [11C]MPDX was not altered. CONCLUSIONS: The axon degeneration related decrease of the AA(1) receptor density resulted in a transient up-regulation of postsynaptic BDZ receptor density in monocularly enucleated adult rats. These results suggest that these radioligands can be used to study the distribution of the postsynaptic BDZ and presynaptic AA(1) receptors in the visual system and can probably be applied to the human visual system for positron emission tomography.

Animals↗

PubMedDate not supplied

Elevated levels of inhibin-A and immunoreactive inhibin in aged male Wistar rats with testicular Leydig cell tumor.

This study was undertaken to investigate the endocrine changes that occur in male Tig:Wistar rats with Leydig cell tumors, with special reference to immunoreactive inhibin (ir-inhibin) and its dimeric forms. Adult male rats from 2 to 28 months of age were used. Blood samples were taken to measure plasma concentrations of ir-inhibin, inhibin-A, inhibin-B, 17beta-estradiol (E2), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Inhibin bioactivity in both peripheral plasma and testicular extracts was also measured. Rats aged 18 months and older had testicular Leydig cell tumor. Testicular tissue sections from 27-month-old rats examined immunohistochemically showed strong positive staining for all 3 inhibin subunits, in particular inhibin alpha and betaA subunits, in the tumor cells. Plasma concentrations of ir-inhibin began to rise significantly (P < .05) at 18 months of age. High bioactivity of inhibin was detected not only in testicular extracts but also in peripheral plasma of aged rats. Thus, plasma concentrations of bioactive inhibin-A, but not inhibin-B, were significantly elevated with increasing age. The concentrations were significantly higher than those in normal male (P < .01) or normal female (P < .05) rats. Plasma concentrations of E2 were significantly (P < .05) elevated only at 23-24 months of age. A marked reduction (P < .05 to .001) in plasma LH and FSH concentrations was observed at 18 months of age and older. Plasma concentrations of testosterone were highest at 2 months of age and then decreased gradually and significantly (P < .05 to .001) afterward. Significant (P < .05 to .001) positive (testosterone vs LH) and negative (ir-inhibin vs FSH, ir-inhibin vs LH, and E2 vs FSH) correlations were observed. It is suggested that plasma inhibin-A levels are elevated in male Tig:Wistar rats with Leydig cell tumor, and thus inhibin-A may be used as a specific marker of testicular Leydig cell tumors. The present results also suggest that the age-related decline in plasma gonadotropins and thus testosterone levels in Tig:Wistar rats may be due to the development of tumors of the Leydig cells rather than to aging per se.

Aging↗