NEUROMODULATION IN MOLLUSCAN SMOOTH-MUSCLE - THE ACTION OF 5-HT, FMRFAMIDE AND PURINE COMPOUNDS

1. The RR, OR, RS and RP muscles of Buccinum did not respond directly to 5-HT, but this monoamine converted their normally tonic ACh respons es to fast twitch contractions with lowered tonic force. This action w as not accompanied by significant membrane potential changes. 2. Pre-t reatment with dibutyryl cAMP potentiated ACh responses and enhanced 5- HT modification of the responses. 3. All muscles responded strongly to FMRFamide with twitch contractions but this was not accompanied by si gnificant membrane potential changes. 4. FMRFamide enhanced ACh contra cture force and converted the responses into fast twitch activity. FMR Famide responses were dramatically inhibited by 5-HT with loss of all tonic force and fast twitch activity. 5. While dibutyryl cAMP did not affect FMRFamide responses, the IP3 inhibitor lithium, at very high co ncentrations, caused a significant diminution of FMRFamide responses. 6. All four muscles were unresponsive to adenosine and ATP but all exc ept the RP responded in a dose-dependent manner to GTP and GTP-gamma-S over the 10(-7)-10(-4) mol l(-1) range. The responses showed moderate fast twitch activity which was unaccompanied by action potential disc harges. Guanosine was without effect, except at very high concentratio ns where it inhibited FMRFamide responses. 7. ACh and GTP acted additi vely to increase muscle force and to enhance ACh-induced depolarizatio n. Similarly both GTP and GTP-gamma-S acted additively, considerably e nhancing FMRFamide responses. 8. It is proposed that 5-HT, FMRFamide a nd GTP may, via their separate receptors or by possible interaction wi th ion channels, activate secondary messenger systems to modify the ca lcium released by ACh-induced depolarization to modulate excitation-co ntraction coupling and force generation in these muscles.