Enkephalin-related peptides: direct action on the octopus heart

Immunocytochemical evidence for the occurrence of "vertebrate" peptides in the neuropil of the vena cava [12, 13] and the structural similarity between enkephalin precursor peptides and the molluscan cardioexcitatory peptide [16], lead us to study the action of enkephalin-related peptides on the octopus heart. Systemic hearts of Octopus vulgaris were perfused with sea wate and test substances and a crude extract of vena cave were added for 1 min; frequency and pressure were monitored continuously. The heptapeptide Leu5-enkephalin-Arg6-Phe7 and the Met5-analogue, both in the amidized form, displayed dose-response relationship with a sensitivity of about 10 nmol. The C-terminal tetrapeptide amides, Phe-Leu/Met-Arg-Phe-NH2, were active at the same doses. Opiate receptors do not seem to be involved in this action on the octopus heart, as naloxone treatment had no effect. Whereas the N-terminal portion of the heptapeptide is known to be crucial for activity as an opioid, the C-terminal NH2 group is essential for cardioexcitatory activity.