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ORIGINAL ARTICLES  CELLULAR AND MOLECULAR ADVANCES IN THE STUDY OF INFLAMMATION


Minerva Biotecnologica 2004 Giugno;16(2):101-8

lingua: Inglese

Binding and func­tion­al char­ac­ter­iza­tion of A3 aden­o­sine recep­tors in ­human neu­troph­ils ­exposed to elec­tro­mag­net­ic ­fields

Varani K. 1, Gessi S. 1, Merighi S. 1, Iannotta V. 1, Cattabriga E. 1, Pancaldi C. 1, Cadossi R. 2, Borea P. A. 1

1 Pharmacology Unit, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy;
2 Laboratory of Biophysics, ­IGEA, Carpi, Italy


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Adenosine medi­ates a num­ber of phys­io­log­i­cal func­tions ­through the inter­ac­tion ­with 4 ­cell sur­face sub­types clas­si­fied as A1, A2A, A2B and A3 recep­tors ­which are cou­pled to G pro­teins. Recently we ­have dem­on­strat­ed ­that ­anti-inflam­ma­to­ry ­actions of aden­o­sine are pro­duced by the involve­ment of A2A and A3 aden­o­sine recep­tor sub­types. In ­human neu­troph­ils A3 recep­tors ­exert ­their ­anti-inflam­ma­to­ry prop­er­ties by inhib­it­ing degran­u­la­tion, chem­o­tax­is and super­ox­ide ­anion pro­duc­tion. Several ­works ­have inves­ti­gat­ed the depen­dence of pro­longed expo­sure to puls­ing elec­tro­mag­net­ic ­fields (PEMFs) on pro­life­ra­tive ­effects and on ­cell den­sity. The ­present ­paper ­describes a sig­nif­i­cant alter­a­tion of A3 aden­o­sine recep­tor den­sity and func­tion­al­ity in ­human neu­troph­ils ­exposed to PEMFs. Saturation bind­ing experi­ments ­were per­formed ­using a ­high affin­ity radio­lig­and antag­o­nist, [3H]-MRE 3008F20, and ­revealed a sig­nif­i­cant ­increase of A3 aden­o­sine recep­tor den­sity in ­PEMF-treat­ed ­human neu­troph­ils. A ther­mo­dy­nam­ic anal­y­sis of [3H]-MRE 3008F20 bind­ing was per­formed ­with the aim of obtain­ing new ­insights ­into the ­effect of PEMFs on the forc­es driv­ing ­drug-recep­tor ­coupling. Competition of radio­lig­and bind­ing by the ­high affin­ity A3 recep­tor ago­nists Cl-IB-­MECA and IB-­MECA in the ­absence and in the pres­ence of PEMFs has ­been per­formed. In func­tion­al ­assays the ­effects of Cl-IB-­MECA and IB-­MECA in the aden­y­lyl ­cyclase activ­ity, in the super­ox­ide ­anion pro­duc­tion and in cal­cium ­release ­have ­been eval­u­at­ed.

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