title: Cyclic-AMP mediated regulation of ABCB mRNA expression in mussel haemocytes.
abstract: BACKGROUND
  The multixenobiotic resistance system (MXR) allows aquatic organisms to cope with their habitat despite high pollution levels by over-expressing membrane and intracellular transporters, including the P-glycoprotein (Pgp). In mammals transcription of the ABCB1 gene encoding Pgp is under cAMP/PKA-mediated regulation; whether this is true in mollusks is not fully clarified.
  
  
  RESULTS
  cAMP/PKA regulation and ABCB mRNA expression were assessed in haemocytes from Mediterranean mussels (Mytilus galloprovincialis) exposed in vivo for 1 week to 0.3 ng/L fluoxetine (FX) alone or in combination with 0.3 ng/L propranolol (PROP). FX significantly decreased cAMP levels and PKA activity, and induced ABCB mRNA down-regulation. FX effects were abolished in the presence of PROP. In vitro experiments using haemocytes treated with physiological agonists (noradrenaline and serotonin) and pharmacological modulators (PROP, forskolin, dbcAMP, and H89) of the cAMP/PKA system were performed to obtain clear evidence about the involvement of the signaling pathway in the transcriptional regulation of ABCB. Serotonin (5-HT) decreased cAMP levels, PKA activity and ABCB mRNA expression but increased the mRNA levels for a putative 5-HT1 receptor. Interestingly, 5-HT1 was also over-expressed after in vivo exposures to FX. 5-HT effects were counteracted by PROP. Forskolin and dbcAMP increased PKA activity as well as ABCB mRNA expression; the latter effect was abolished in the presence of the PKA inhibitor H89.
  
  
  CONCLUSIONS
  This study provides the first direct evidence for the cAMP/PKA-mediated regulation of ABCB transcription in mussels.
authors.affiliation: Interdepartment Centre for Environmental Science Research, University of Bologna, Ravenna, Italy. silvia.franzellitti@unibo.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Franzellitti
authors.forename: Elena
authors.initials: E
authors.lastname: Fabbri
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006434:Hemocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008954:Models, Biological; D049878:Mytilus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D009638:Norepinephrine / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007546:Isoquinolines; D012333:RNA, Messenger; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D005473:Fluoxetine; D005576:Colforsin; D012701:Serotonin; D003994:Bucladesine; D011433:Propranolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D009638:Norepinephrine