MODULATORY MECHANISMS IN THE ISOLATED INTERNALLY PERFUSED VENTRICLE OF THE WHELK BUSYCON CANALICULATUM

1. Isolated cannulated ventricles commenced spontaneous beating on app lication of perfusion pressure of 10 cm water. Complete hearts showed a fast patterned cyclical rhythm, whereas ventricles devoid of atrial material showed a continuous slow rhythm. 2. Perfused ventricles were inhibited by ACh with a threshold at 10(-8) mol l(-1) and arrested at 10(-7) mol l(-1), and ventricles under stimulation by 5HT could be arr ested by ACh at this concentration. 3. Perfused ventricles were stimul ated by 5HT, with threshold at 10(-9) mol l(-1) and maximum at 10(-5) mol l(-1). Metoclopramide was without affect on 5HT responses, but met itipine and methysergide did inhibit such responses suggesting that th e 5HT receptor present possessed mixed properties of the vertebrate 5- HT1 and 5-HT2 receptor subtypes. 4. Ventricles were very sensitive to the excitatory actions of FMRFamide in the 10(-9) to 10(-5) mol l(-1) range. Preparations were insensitive to GAPFLRFamide, but SCP-B was mo destly excitatory (threshold 10(-7) mol l(-1)). 5. Preparations were n ot significantly affected by adenosine, ATP, and guanosine, but GTP wa s strongly excitatory at 10(-7) mol l(-1). 6. 5HT and FMRFamide respon ses were additive. Preparations responded strongly to the adenylate cy clase activator forskolin and dibutyryl cAMP enhanced spontaneous cont ractions and 5HT responses, suggesting that the 5HT receptor may opera te via a cAMP secondary mechanism. 7. The IP3 inhibitor lithium (10 mm ol l(-1)), caused slight inhibition of FMRFamide responses, suggesting that the receptor to this peptide may operate via IP3 as a second mes senger. 8. Neuromodulation in this preparation would appear to involve ACh as inhibitor, 5HT and FMRFamide as upregulators, with no clear ro les for FMRFamide-related peptides and GTP.