NITRIC-OXIDE MEDIATES THE INHIBITORY EFFECTS OF SDPNFLRFAMIDE, A NEMATODE FMRFAMIDE-RELATED NEUROPEPTIDE, IN ASCARIS-SUUM

1. The physiological effects of two Phe-Met-Arg-Phe-NH2 (FMRFamide)-re lated neuropeptides isolated from the free-living nematode Panagrellus redivivus, SDPNFLRFamide (PF1) and SADPNFLRFamide (PF2), were examine d using neuromuscular preparations from the parasitic nematode Ascaris suum. 2. PF1 and PF2 hyperpolarized muscle membrane and induced susta ined flaccid paralysis, independent of external Cl-, in both innervate d and denervated preparations. 3. PF1 reversed spastic contractions in duced by the cholinomimetic levamisole, elevated K+, or the excitatory nematode FMRFamide-related neuropeptides KNEFIRFamide or KHEYLRFamide . 4. PF1 reversal of levamisole contraction was blocked by pre treatme nt with agents that interfere with nitric oxide (NO) synthesis (e.g., N-nitro-L-arginine), whereas sodium nitroprusside, which releases NO i n solution, mimicked PF1 and PF2. 5. NO synthase activity, monitored b y the conversion of [H-3]arginine to [H-3]citrulline, was twice as abu ndant in A. suum hypodermis as in muscle, but was not present in repro ductive tissue. The relative abundance of NO synthase activity in thes e tissues was similar to the observed specific binding of [H-3]PF1. 6. These results suggest that the inhibitory effects of PF1 and PF2 on n ematode somatic muscle are mediated by NO, and that the hypodermis may serve a role in this process analogous to that of the endothelium in vertebrate vasculature.