1. The physiological effects of two
Phe-Met-Arg-Phe-NH2 (
FMRFamide)-related
neuropeptides isolated from the free-living nematode Panagrellus redivivus,
SDPNFLRFamide (PF1) and
SADPNFLRFamide (PF2), were examined using neuromuscular preparations from the parasitic nematode Ascaris suum. 2. PF1 and PF2 hyperpolarized muscle membrane and induced sustained flaccid
paralysis, independent of external Cl-, in both innervated and denervated preparations. 3. PF1 reversed
spastic contractions induced 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 pretreatment with agents that interfere with
nitric oxide (NO) synthesis (e.g., N-nitro-
L-arginine), whereas
sodium nitroprusside, which releases NO in
solution, mimicked PF1 and PF2. 5.
NO synthase activity, monitored by the conversion of [3H]
arginine to [3H]
citrulline, was twice as abundant in A. suum hypodermis as in muscle, but was not present in reproductive tissue. The relative abundance of
NO synthase activity in these tissues was similar to the observed specific binding of [3H]PF1. 6. These results suggest that the inhibitory effects of PF1 and PF2 on nematode 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.