THE EFFECTS OF THE PEPTIDES AF3 (AVPGVLRFAMIDE) AND AF4 (GDVPGVLRFAMIDE) ON THE SOMATIC MUSCLE OF THE PARASITIC NEMATODES ASCARIS-SUUM AND ASCARIDIA-GALLI

AF3 (AVPGVLRFamide) and AF4 (GDVPGVLRFamide) are endogenous RFamide-li ke peptides isolated from the parasitic nematode Ascaris suum. Here th e actions of these peptides on the somatic musculature of Ascaris have been investigated and compared to the action of acetylcholine (ACh), the excitatory transmitter at the neuromuscular junction. ACh, AF3 and AF4 contracted muscle with EC(50)s of 13 +/- 1 mu M, 24 +/- 6 nM and 37 +/- 2 nM, respectively (n = 6). The muscle cells were depolarized b y ACh (3 mu M; 5.2 +/- 0.4 mV, n = 42), AF3 (1 mu M; 2.6 +/- 0.3 mV, n = 19) and AF4 (1 mu M; 3.3 +/- 0.4 mV, n = 19). EC(50)s were 681 +/- 329 nM (AF3) and 901 +/- 229 nM (AF4), but an estimate could not be ma de for ACh due to muscle contraction at concentrations greater than 10 mu M. The depolarization to 3 pan ACh was abolished by the nicotinic receptor antagonist mecamylamine (10 mu M; n = 5) but the responses to the peptides were not (111 +/- 7 % and 108 +/- 17 % with respect to c ontrol; n = 5). The depolarization elicited by ACh was reduced to a gr eater extent by a 50 % reduction in extracellular Na+ concentration th an the response to AF3 and AF4 (P < 0.02). Cobalt was more effective a t blocking the AF3 and AF4 depolarizations than those to ACh. These ob servations suggest that AF3 and AF4 contract Ascaris muscle without an action at the Ascaris nicotinic receptor. Furthermore, the ionic mech anism through which AF3 and AF4 depolarize Ascaris muscle is different from that for ACh. ACh, AF3 and AF4 were also found to contract Ascar idia galli somatic muscle with EC(50)s of 13 +/- 3 mu M, 721 +/- 236 n M and 371 +/- 177 nM, respectively (n = 7). The muscle cells were depo larized by ACh (EC50 = 14 +/- 5 mu M, n = 5), AF3 (EC50 = 5 +/- 3 mu M , n = 4) and AF4 (EC50 = 10 +/- 5 mu M, n = 4). Therefore the response to these peptides is not unique to Ascaris and the) may subserve a fu nctional role in the motor nervous system of parasitic nematodes.