MODULATING A MODULATOR - BIOGENIC-AMINES AT SUBTHRESHOLD LEVELS POTENTIATE PEPTIDE-MEDIATED CARDIOEXCITATION OF THE HEART OF THE TOBACCO HAWKMOTH MANDUCA-SEXTA

The central nervous system of the moth Manduca sexta contains a group of myoregulatory neuropeptides, the CAPs (Cardioacceleratory Peptides), which cause a physiologically important, dose-dependent increase in heart rate during wing inflation and flight in adult moths. We report here that the response of the adult heart to a subset of the CAPs, the CAP(2)s, is potentiated nearly twofold in the chronic presence of subthreshold levels of the biogenic amine octopamine or near-threshold levels of the biogenic amine serotonin. Subthreshold levels of the CAP(2)s fail to alter the response of the heart to octopamine. We have begun to investigate the molecular mechanisms underlying this potentiation. Previous work on the adult heart has shown that the CAP(2)s act through an inositol-1,4,5-trisphosphate second-messenger system. Here, we demonstrate that the cardioexcitatory effects of the two amines, in contrast to those of the CAP(2)s, are both mediated by cyclic AMP. Application to the heart of either 10(-5) mol l(-1) octopamine or 10(-6) mol l(-1) serotonin elicits a threefold increase in intracellular cyclic AMP levels. The CAP(2)s have no effect on cyclic AMP levels in the heart. These results illustrate a mechanism by which the effectiveness of a neurohormone can be increased with minimal cost to the animal. In Manduca sexta, subthreshold levels of octopamine are found in the haemolymph during wing inflation and flight. Thus, it is possible that octopamine up-regulates the effects of CAP(2) via a cyclic-AMP-dependent mechanism during these activities.