Inhibition of tyramine signaling by cGMP in Drosophila Malpighian tubules

Abstract

The Malpighian tubules are secretory epithelia that serve as the proximal component of the insect excretory system. The biogenic amine tyramine (TA) acts as a diuretic in Drosophila tubules by increasing transepithelial chloride conductance through a mechanism that requires an increase in intracellular calcium levels. The second messenger cGMP has previously been shown to cause diuresis by enhancing active transepithelial cation transport (Kerr et al., Curr. Biol., 2004). We tested the hypothesis that cGMP also affects the TA signaling pathway. Treatment of tubules with 1mM cGMP for 4 to 5 minutes resulted in a significant inhibition of the depolarizing response to both 10nM TA (80% suppression) and 100nM TA (18% suppression). Sensitivity to the diuretic peptide leucokinin (LK), which acts similarly to TA, was also inhibited by cGMP (38% suppression of response to 100pM LK). These data reveal the presence of some mechanism for cGMP‐mediated inhibition of diuretic signaling that is downstream of the TA receptor. We are currently investigating the involvement of specific cGMP‐dependent protein kinase isoforms in this modulation. Supported by NSF 0744619 to E.M.B.