NPR-2 is a C. elegans neuropeptide-Y like (NPY) receptor. Previous work has demonstrated that both gene deletion and RNAi targeting for NPR-2 results in defective locomotion (Keating et al. 2003 Curr Biol. 13: 1715-20). NPR-2 is widely expressed in the nervous system, including the pharyngeal nervous system. We therefore hypothesised that NPR-2 may also play a role in the regulation of pharyngeal pumping. To investigate this possibility we have made both extracellular and intracellular electrophysiological recordings from the pharyngeal muscle of npr mutant and wild-type animals. Comparison of N2 and
npr-2(
ok419) animals revealed a significantly lower basal rate of pumping in the mutant coupled with a reduced sensitivity to 5-HT. NPR-1 is the most closely related receptor to NPR-2 and is also expressed in the pharyngeal nervous system. The reduction in basal pumping and 5-HT sensitivity were suppressed in an
npr-2(
ok419);
npr-1(
ky13) double mutant. This has also been noted with regards to the locomotor defect of
npr-2(
ok419) and suggests an antagonistic interaction between the signalling pathways in which these genes are active. As the neuropeptides FLP-18 and FLP-21 have previously been identified as ligands for NPR-1 (Rogers et al. 2003 Nat Neurosci 6: 1178-85) we tested the response of the npr mutants to exogenous addition of these peptides. Exogenous application of either FLP-18A or FLP-21 (1M) inhibits pharyngeal pumping. The inhibitory response to FLP-21 but not FLP-18A, is absent in
npr-2(
ok419). However,
npr-1(
ky13) responds to both peptides similarly to wild-type animals. The double mutant
npr-2(
ok419);
npr-1(
ky13) behaves similarly to
npr-2(
ok419) i.e. the inhibitory response to FLP-21 is absent. This indicates that although
npr-1(
ky13) suppresses the effect of
npr-2(
ok419) on pharyngeal pumping, it does not suppress the abolition of the response to FLP-21. Furthermore, it would appear that
npr-2, but not
npr-1 is required for the pharyngeal response to exogenous FLP-21. Currently we are testing the hypothesis that FLP-21 directly activates NPR-2 in the pharyngeal nervous system.. Funded by the BBSRC, UK. Thanks to Mario De Bono and the C. elegans knockout consortia (NBRP Japan and USA) for the provision of strains.