title: Calcineurin is part of a negative feedback loop in the InsP3/Ca²⁺ signalling pathway in blowfly salivary glands.
abstract: The ubiquitous InsP3/Ca(2+) signalling pathway is modulated by diverse mechanisms, i.e. feedback of Ca(2+) and interactions with other signalling pathways. In the salivary glands of the blowfly Calliphora vicina, the hormone serotonin (5-HT) causes a parallel rise in intracellular [Ca(2+)] and [cAMP] via two types of 5-HT receptors. We have shown recently that cAMP/protein kinase A (PKA) sensitizes InsP3-induced Ca(2+) release. We have now identified the protein phosphatase that counteracts the effect of PKA on 5-HT-induced InsP3/Ca(2+) signalling. We demonstrate that (1) tautomycin and okadaic acid, inhibitors of protein phosphatases PP1 and PP2A, have no effect on 5-HT-induced Ca(2+) signals; (2) cyclosporin A and FK506, inhibitors of Ca(2+)/calmodulin-activated protein phosphatase calcineurin, cause an increase in the frequency of 5-HT-induced Ca(2+) oscillations; (3) the sensitizing effect of cyclosporin A on 5-HT-induced Ca(2+) responses does not involve Ca(2+) entry into the cells; (4) cyclosporin A increases InsP3-dependent Ca(2+) release; (5) inhibition of PKA abolishes the effect of cyclosporin A on the 5-HT-induced Ca(2+) responses, indicating that PKA and calcineurin act antagonistically on the InsP3/Ca(2+) signalling pathway. These findings suggest that calcineurin provides a negative feedback on InsP3/Ca(2+) signalling in blowfly salivary glands, counteracting the effect of PKA and desensitizing the signalling cascade at higher 5-HT concentrations.
authors.affiliation: Institute of Biochemistry and Biology, Department of Animal Physiology, University of Potsdam, Karl-Liebknecht-Str. 24/25, 14476 Potsdam, Germany.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Heindorff
authors.affiliation: Institute of Biochemistry and Biology, Department of Animal Physiology, University of Potsdam, Karl-Liebknecht-Str. 24/25, 14476 Potsdam, Germany. Electronic address: obaumann@uni-potsdam.de.
authors.forename: Otto
authors.initials: O
authors.lastname: Baumann
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002147:Calmodulin / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004175:Diptera; D025461:Feedback, Physiological; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002147:Calmodulin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin; D002118:Calcium
keywords: Blowfly; Ca(2+); Ca(2+) oscillations; Calcineurin; Insect; Intracellular signalling; Protein kinase A; Salivary gland; cAMP