Fluid secretion in the salivary gland of the blowfly, Calliphora vicina, is induced by the neurohormone serotonin (5-HT). 5-HT, simultaneously, activates the InsP₃/Ca²⁺- and the cAMP-signaling pathways, whereby threshold concentrations of 5-HT induce intracellular Ca²⁺-oscillations and intercellular Ca²⁺-waves. We studied the influence of cAMP on the spatiotemporal pattern of the Ca²⁺-oscillations and -waves, using isolated glands loaded with the Ca²⁺-sensitive fluorescent dye Fura-2.

We found: (1) Cinanserin, a selective inhibitor of the 5-HT receptor that couples to the cAMP signaling pathway, leads to a significant decrease in the frequency of intracellular Ca²⁺-oscillations induced by threshold concentrations of 5-HT.

(2) In the presence of cinanserin, the normal frequency of the 5-HT-induced Ca²⁺-oscillations can be reconstituted by addition of the membrane-permeable cAMP analog 8-CPT-cAMP. (3) The PKA inhibitor Rp-8-CPT-cAMPS mimics the effects of cinanserin. This indicates that the influence of cAMP on intracellular Ca²⁺-oscillations is mediated by PKA.

(4) The inhibition of 5-HT-induced cAMP formation by cinanserin, the addition of 8-CPT-cAMP in the presence of cinanserin, or PKA-inhibition by Rp-8-CPT-cAMPS affect the spatial pattern of the Ca²⁺-signals as well: our findings indicate that, depending on the intracellular cAMP-concentration, either spatially non-synchronized oscillations, intercellular waves, and/or global beating is observed.

This suggests that the delicate balance between the parallel activation of the InsP₃/Ca²⁺- and the cAMP-signaling pathways affects the spatiotemporal pattern of intracellular Ca²⁺-signaling strongly. These observations supplement our previous findings that cAMP sensitizes, via PKA, InsP₃-induced Ca²⁺ release from the ER.

Supported by the DFG, Wa 463/9.