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11.
Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists. 总被引:4,自引:0,他引:4
Renzo Cescato Stefan Schulz Beatrice Waser Véronique Eltschinger Jean E Rivier Hans-Jürgen Wester Michael Culler Mihaela Ginj Qisheng Liu Agnes Schonbrunn Jean Claude Reubi 《Journal of nuclear medicine》2006,47(3):502-511
The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications. 相似文献
12.
Carlo Piccinni Chiara Sacripanti Elisabetta Poluzzi Domenico Motola Lara Magro Ugo Moretti Anita Conforti Nicola Montanaro 《European journal of clinical pharmacology》2010,66(2):199-206
Aim
The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence. 相似文献13.
B. Bagolini V. Porciatti B. Falsini G. Scalia M. Neroni G. Moretti 《Documenta ophthalmologica. Advances in ophthalmology》1988,70(1):37-43
Macular and paramacular electroretinograms in response to two adjacent checks (6 deg/side), alternating at constant mean luminance, were recorded in 34 normal subjects ranging in age from 16 to 74 years. The macular electroretinogram declines progressively in amplitude with age (R = –0.42; P = 0.013). The amplitude ratio between macular and paramacular responses tends to be independent of age (R = -0.21; P = 0.22).Age-related changes in the macular electroretinogram shown in our study are consistent with previous anatomical and functional studies, which indicate a deterioration of photoreceptors beyond 20 years of age. These results suggest a possible use of this technique for future studies on macular degeneration. 相似文献
14.
A. Conforti R. Leone U. Moretti L. Guglielmo G. P. Velo 《Pharmacoepidemiology and drug safety》1995,4(3):129-135
Pharmacovigilance started in Italy in 1965, and from 1987 reporting of ADRs has been mandatory. Doctors have to send the filled forms on suspected ADRs to the Local Health Districts which transmit biannually all the reports to the Health Department. In a Northern Italian Region (Veneto) spontaneous reporting of adverse drug reactions (ADRs) has been studied during the period 1988–1993. This Region contributes a substantial percentage of the total Italian reports. The total number of reports was 3700, most of these (54 per cent) coming from GPs. A great variability in the reporting rate among the 36 districts of Veneto Region (range: 0–8.8 per 10,000 inhabitants per year) and an important under-reporting have been evident. Underreporting is also emphasized by the fact that in 1993 the Veneto doctors who sent at least one report were only 2.7 per cent. On the whole about 35 per cent of reports concerned minor reactions caused by drugs which have a well known toxicological profile. Comparison between reports coming from Veneto and the UK in some cases show a similar safety profile (omeprazole and simvastatin), whereas in other cases (e.g. terfenadine, glafenine, fluoxetine) no correspondence can be found. This article reveals the limits of the actual spontaneous reporting in Italy and suggests some possible measures for improving it. 相似文献
15.
Pattern electroretinogram as a function of spatial frequency in ocular hypertension and early glaucoma 总被引:6,自引:0,他引:6
V. Porciatti B. Falsini S. Brunori A. Colotto G. Moretti 《Documenta ophthalmologica. Advances in ophthalmology》1987,65(3):349-355
Pattern electroretinograms (PERGs) in response to 8.3 Hz alternating gratings (16.6 rev/sec) of different spatial frequencies were recorded in normal subjects as well as in patients affected by early glaucoma and ocular hypertension. In normal subjects the PERG response is spatially tuned, with a maximum at about 1.5 cycles/deg and attenuation at higher and lower spatial frequencies. In all cases of early glaucoma and in the great majority of cases of ocular hypertension the PERG was reduced, as compared with that of normal subjects, mainly in the medium range of spatial frequencies (at which the PERG has its maximal amplitude). 相似文献
16.
A Bitti P Mastrantonio P Spigaglia G Urru A I Spano G Moretti G B Cherchi 《Journal of clinical pathology》1997,50(3):259-260
Clostridium sordellii is an infrequent human pathogen. It has been demonstrated to be occasionally responsible for myonecrosis or gas gangrene. Interestingly, in the obstetric literature, some cases of postpartum maternal deaths have been associated with C sordellii infection causing a rapidly lethal toxin mediated syndrome. This is the first reported case of postpartum death in a 29 year old woman, in which a toxigenic C sordellii was isolated from the patient's blood antemortem during the fatal toxic shock, strongly indicating its role in this rare syndrome. 相似文献
17.
F Brée G Houin J Barré J L Moretti V Wirquin J P Tillement 《Clinical pharmacokinetics》1986,11(4):336-342
The volumes of distribution of many acidic drugs have been shown to be close to that of their binding protein, i.e. serum albumin. The distribution of basic drugs mainly bound to alpha 1-acid glycoprotein (AAG) can be questioned with respect to its dependency upon the distribution of this plasma protein. So, a pharmacokinetic study was performed in 7 subjects with human 125I-labelled alpha 1-acid glycoprotein. The steady-state volume of distribution was found to be 5.37 +/- 0.82L. The central volume was 3.23 +/- 0.33L, close to that of plasma volume and the peripheral volume was 2.14 +/- 0.63L. These data allowed the establishment of an equation giving access to the volume of distribution of a basic drug by relating its unbound fraction to physiological distribution of alpha 1-acid glycoprotein. The values yielded by this equation show that the actual and calculated volumes of distribution of basic drugs mainly bound to AAG are discrepant. This protein is thus not the main factor controlling the distribution of basic drugs within the body. 相似文献
18.
Zingraff J.; Caillat-Vigneron N.; Urena P.; Gagne E.-R.; Bererhi L.; Moretti J.-L.; Bardin T.; Drueke T. B. 《Nephrology, dialysis, transplantation》1995,10(2):223-229
Dialysis amyloidosis is one of the most incapacitating complicationsof long-term dialysis treatment. Quantitative assessment ofamyloid deposition using radiolabelled tracers has been recentlyproposed but convincing evidence of its validity in uraemicpatients remains to be provided. We studied the plasma kineticsof i.v. administered 125I-labelled serum amyloid P component(125I-SAP) in 20 chronic haemodialysis patients compared withthose of nine healthy volunteers and three non-dialysed patientswith systemic amyloidosis. Plasma clearance of the tracer wasabnormal in 17 of 20 dialysis patients in whom plasma radioactivitydeclined in a bi-exponential mode, in contrast to the single-exponentialslope observed in all healthy controls. 125I-SAP plasma half-lifeof the second component, probably reflecting metabolic clearance,was significantly prolonged in these dialysis patients comparedwith the healthy controls (35.3 versus 24.6 h, P<0.001).Among the long-term haemodialysis patients the calculated extravasculardistribution of 125I-SAP was significantly greater in thosewith severe arthropathy than in asymptomatic patients. Thesefindings demonstrate for the first time that SAP clearance isdisturbed in haemodialysis patients due to both failing renalelimination and retention in extravascular sites. The extravasculardiffusion is greatly enhanced in patients with clinical evidenceof amyloidosis. Therefore the study of plasma 125I-SAP kineticspromises to be a valuable tool to quantitate the extent of amyloidosis. 相似文献
19.
Rainaldi Giuseppe; Meneveri Raffaella; Mariani Laura; Ginelli Enrico; Moretti Arcangela; Vatteroni Lucia 《Mutagenesis》1996,11(4):401-404
Clone CSA7 is a CHEF18 hamster cell line that shows an increasedintracellular accumulation of dCTP. To localize the mutationsthat accumulate spontaneously in a functional gene of such amutator phenotype, independent CSA7 mutants of the hypoxanthineguaninephosphoribosyl transferase (hprt) gene were isolated and screenedby a polymerase chain reactionsingle strand conformationpolymorphism technique. Sixty-two percent of mutants produceddetectable changes of the strand migration profile and the mutationswere preferentially localized in the exons 3 (31%) and 6 (62%).The sequencing of such exons revealed that the rate of C baseincorporation was the major mutation pathway and that the Abase of a GGA sequence was the preferential site of misincorporation.
3To whom correspondence should be addressed 相似文献
20.