The NHE family of Na+/H+ exchangers is believed to play an essential role i
n animals, but may play an additional, specialised epithelial role in insec
ts. The pharmacological sensitivity of the Drosophila melanogaster Malpighi
an tubule to a range of amiloride derivatives was shown to be consistent wi
th an effect on an exchanger, rather than a Na+ channel. Consistent with th
is, no degenerin/epithelial Na+ channel (ENaC) genes could be detected in M
alpighian tubules by reverse transcriptase/polymerase chain reaction (RT-PC
R). Using a low-stringency homology searching, three members of the NHE fam
ily were identified in the genomic sequence of Drosophila melanogaster, alt
hough only two genes were represented as expressed sequence tags. All three
genes (DmNHE1 at cytological position 21B1, DmNHE2 at 39B1 and DmNHE3 at 2
7A1) were found by RT-PCR to be widely expressed, and one (DmNHE2) was show
n to have multiple transcripts. The putative translations of the three gene
s mark them as distantly related members of the family, inviting the possib
ility that they may serve distinct roles in insects.