cAMP potentiates InsP3-induced Ca2+ release from the endoplasmic reticulum in blowfly salivary glands.
BACKGROUND
Serotonin induces fluid secretion from Calliphora salivary glands by the parallel activation of the InsP3/Ca2+ and cAMP signaling pathways. We investigated whether cAMP affects 5-HT-induced Ca2+ signaling and InsP3-induced Ca2+ release from the endoplasmic reticulum (ER).


RESULTS
Increasing intracellular cAMP level by bath application of forskolin, IBMX or cAMP in the continuous presence of threshold 5-HT concentrations converted oscillatory [Ca2+]i changes into a sustained increase. Intraluminal Ca2+ measurements in the ER of beta-escin-permeabilized glands with mag-fura-2 revealed that cAMP augmented InsP3-induced Ca2+ release in a concentration-dependent manner. This indicated that cAMP sensitized the InsP3 receptor Ca2+ channel for InsP3. By using cAMP analogs that activated either protein kinase A (PKA) or Epac and the application of PKA-inhibitors, we found that cAMP-induced augmentation of InsP3-induced Ca2+ release was mediated by PKA not by Epac. Recordings of the transepithelial potential of the glands suggested that cAMP sensitized the InsP3/Ca2+ signaling pathway for 5-HT, because IBMX potentiated Ca2+-dependent Cl- transport activated by a threshold 5-HT concentration.


CONCLUSIONS
This report shows, for the first time for an insect system, that cAMP can potentiate InsP3-induced Ca2+ release from the ER in a PKA-dependent manner, and that this crosstalk between cAMP and InsP3/Ca2+ signaling pathways enhances transepithelial electrolyte transport.
Schmidt
Ruth
R
Institute of Biochemistry and Biology, Department of Animal Physiology, University of Potsdam, Karl-Liebknecht-Str, 24-25, 14476 Potsdam-Golm, Germany. r.schmidt@medice.de
Baumann
Otto
O
Walz
Bernd
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000008:administration & dosage*; D004175:Diptera / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000008:administration & dosage*; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D012701:Serotonin; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D002118:Calcium