The cAMP response to isoprenaline in mononuclear cells is markedly increased in the presence of platelets.
We have previously shown that the addition of platelets to mononuclear cells (MNC) increases cAMP in MNC. This response may be of interest because the physical interaction between platelets and MNC plays an important role in the inflammatory process. We have now demonstrated that the addition of both isoprenaline and platelets to MNC resulted in a marked amplification of the cAMP response. Prostaglandins, ATP and adenosine and the P-selectin ligand PSGL-1 could not account for the response. No substance was found in the supernatant that could increase cAMP in MNC. W7, a Ca(2+)-calmodulin inhibitor and the addition of EDTA reduced the response to both platelets and isoprenaline. Furthermore, we have demonstrated that mRNA for type I adenylyl cyclase, which is sensitive to Ca(2+), is present in MNC. No increase in Ca(2+) in the cytoplasma in MNC was recorded, however, by quantitative fluorescence microscopy after addition of platelets to MNC. It is possible that there are small increments in Ca(2+) at the binding sites, which we were unable to detect by our technique. Alternatively the binding of platelets to MNC may induce intermolecular interactions in the cell membrane which may facilitate the synthesis of cAMP.
Christensen
Niels J
NJ
Department of Endocrinology, Herlev University Hospital, Denmark. nijc@herlevhosp.kbhamt.dk
Bratholm
Palle
P
D000262:Adenylyl Cyclases / Q000235:genetics; D001792:Blood Platelets / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; D007545:Isoproterenol; D002118:Calcium