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Evidence for FMRF-amide as a neurotransmitter in the gill of Aplysia californica

In Aplysia californica, multiple regulatory mechanisms are involved in the actions of neurotransmitters on the gill. Neurotransmitter receptors and adenylate cyclase were examined in a particulate fraction of gill homogenates. The neuropeptide FMRF-amide stimulated enzyme activity 7- to 8-fold (EC50, 1 microM) via receptors that were pharmacologically distinct from those for dopamine and serotonin. FMRF- amide augmented cyclic AMP levels in slices of gill tissue with a time course similar to that for adenylate cyclase activation. Increases in cyclic AMP levels produced by the neuropeptide were potentiated by the phosphodiesterase inhibitor theophylline. Physiological responses to neuropeptides and cyclic AMP analogues were examined in a perfused, isolated gill preparation. Phasic contractions evoked by FMRF-amide (EC50, 0.1 microM) were mimicked by membrane-permeable analogues of cyclic AMP. Comparison of FMRF-amide effects on adenylate cyclase and gill behavior suggests an association between cyclic AMP and phasic contractions. In addition, FMRF-amide-like immunoreactivity, detected by antisera raised against the neuropeptide, was found in nerve fibers innervating the gill. These findings indicate that in Aplysia, FMRF- amide or a closely related peptide neurotransmitter may be involved in the physiological regulation of gill behavior.