TY  - JOUR
A1  - Heindorff, Kristoffer
A1  - Baumann, Otto
T1  - Calcineurin is part of a negative feedback loop in the InsP(3)/Ca2+ signalling pathway in blowfly salivary glands
JF  - Cell calcium
N2  - The ubiquitous InsP(3)/Ca2+ signalling pathway is modulated by diverse mechanisms, i.e. feedback of Ca2+ 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 [Ca2+] and [cAMP] via two types of 5-HT receptors. We have shown recently that cAMP/protein kinase A (PKA) sensitizes InsP(3)-induced Ca2+ release. We have now identified the protein phosphatase that counteracts the effect of PKA on 5-HT-induced InsP(3)/Ca2+ signalling. We demonstrate that (1) tautomycin and okadaic acid, inhibitors of protein phosphatases PP1 and PP2A, have no effect on 5-HT-induced Ca2+ signals; (2) cyclosporin A and FK506, inhibitors of Ca2+/calmodulin-activated protein phosphatase calcineurin, cause an increase in the frequency of 5-HT-induced Ca2+ oscillations; (3) the sensitizing effect of cyclosporin A on 5-HT-induced Ca2+ responses does not involve Ca2+ entry into the cells; (4) cyclosporin A increases InsP(3)-dependent Ca2+ release; (5) inhibition of PKA abolishes the effect of cyclosporin A on the 5-HT-induced Ca2+ responses, indicating that PKA and calcineurin act antagonistically on the InsP(3)/Ca2+ signalling pathway. These findings suggest that calcineurin provides a negative feedback on InsP(3)/Ca2+ signalling in blowfly salivary glands, counteracting the effect of PKA and desensitizing the signalling cascade at higher 5-HT concentrations. (C) 2014 Elsevier Ltd. All rights reserved.
KW  - Calcineurin
KW  - Ca2+
KW  - Ca2+ oscillations
KW  - cAMP
KW  - Protein kinase A
KW  - Intracellular signalling
KW  - Salivary gland
KW  - Blowfly
KW  - Insect
Y1  - 2014
U6  - https://doi.org/10.1016/j.ceca.2014.07.009
SN  - 0143-4160
SN  - 1532-1991
VL  - 56
IS  - 3
SP  - 215
EP  - 224
PB  - Churchill Livingstone
CY  - Edinburgh
ER  -