<I>Drosophila melanogaster</I> Malpighian tubules, the fastest transporting epithelia known to date, are an ideal model for studying regulation of fluid secretion. My main discoveries using Oregon R strain tubules were as follows. I showed that ouabain, an inhibitor of Na<SUP>+</SUP>/K<SUP>+</SUP>-ATPase had no effect on tubules' fluid secretion. Octopamine, which stimulates tubules of several other insect species, had no stimulatory effect on these tubules. I discovered that <I>Drosophila</I> tubules are sensitive to much lower concentrations of cAMP than any other known insect. I found differential sensitivity of the posterior and anterior tubules to cAMP. Using radioactive labelling experiments, I found the presence of a cotransporter for cAMP and cGMP on the principal cells' membranes. I proved that tubules are sensitive to very low levels of cGMP. Using membrane permeant analogues of cAMP and cGMP, namely 8-Br-cAMP and 8-Br-cGMP, I discovered that there is a cAMP signalling pathway, but no cGMP pathway, within the secondary "stellate" cells of Oregon R <I>Drosophila melanogaster</I>. I proved that Oregon R tubules are sensitive to extremely low concentrations of cardioacceleratory peptide CAP<SUB>2b</SUB>. I used the recently discovered naturally occurring <I>Drosophila melanogaster</I> mutants with over expressed cGMP-dependent protein kinase ("Forager R") and under expressed cGMP-dependent protein kinase ("Forager S" and "Forager S2") to analyse regulatory mechanisms of fluid secretion. I found that mutants with under expressed cGMP-dependent protein kinase were, in fact, much more responsive to cGMP, to CAP<SUB>2b</SUB> and extremely responsive to cAMP compared with Oregon R tubules. I showed that mutants with over expressed cGMP-dependent protein kinase were less responsive to cGMP, CAP<SUB>2b</SUB> and to cAMP than Oregon R tubules. Thus, both the cAMP and cGMP pathways were affected by the mutation regarding expression of cGMP-dependent protein kinase., I speculate that phosphodiesterase may be affected by under expression or over expression of cGMP-dependent protein kinase, thereby actually overcompensating for the naturally occurring mutation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:597223 |
| Date | January 1998 |
| Creators | Caldwell, F. M. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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