Cyclic AMP is involved in cardioregulation by multiple neuropeptides encoded on the FMRFamide gene

We have used a combination of biochemical and pharmacological techniques to investigate the role of the cyclic nucleotides, 3',5'-cyclic adenosine mon ophosphate (cyclic AMP) and 3',5'-cyclic guanosine monophosphate (cyclic GM P), in mediating the cardioregulatory effects of FMRFamide and other neurop eptides encoded on exon II of the FMRFamide gene of Lymnaea stagnalis, The 'isoleucine' peptides (EFLRIamide and pQFYRIamide) produced complex biphasi c effects on the frequency, force of contraction and tonus of the isolated heart of L. stagnalis, which were dependent on adenylate cyclase (AC) activ ity of the heart tissue, At a control rate of cyclic AMP production of less than or equal to 10 pmoles min(-1) m(-1) protein, the 'isoleucine' peptide s produced a significant increase in AC activity in heart membrane preparat ions, This suggested that the enhanced AC activity is responsible for the s timulatory effects of the 'isoleucine' peptides on frequency and force of c ontraction of heart beat. This excitation sometimes followed an initial 'in hibitory phase' where the frequency of beat, force of contraction and tonus of the heart were reduced by the 'isoleucine' peptides, Hearts that showed the inhibitory phase of the 'isoleucine' response, but characteristically lacked the delayed excitatory phase, were found to have high levels of memb rane AC activity greater than or equal to 10 pmoles min(-1) mg(-1) protein in controls. Application of the 'isoleucine' peptides to membrane homogenat e preparation from these hearts failed to increase AC activity, The additio n of FMRFamide produced significant increases in the rate of cyclic AMP pro duction in the heart membrane preparations, which could account, at least i n part, for the cardioexcitatory effects of this peptide in the isolated wh ole heart, A membrane-permeable cyclic AMP analogue (8-bromo-cyclic AMP) an d an AC activator (forskolin) were also cardioexcitatory, The peptide SEEPL Y had no effects on the beat properties of the isolated heart and did not a lter AC activity, The activity of the membrane-bound (particulate) guanylat e cyclase (GC) was not significantly affected by any of the peptides.