R15α1 and R15α2 peptides from Aplysia: Comparison of bioactivity,distribution, and function of two peptides generated by alternative splicing

The mRNA precursor encoded by the R15 gene is alternatively spliced in different neurons to form two related variants, R15-1 and R15-2 mRNA. One of the peptides encoded by the R15-2 mRNA, the R15α1 peptide, is expressed in the endogenously bursting neuron R15 and mediates some of its central and peripheral synaptic actions. In this study we found that the R15α2 peptide, which is encoded by the R15-1 mRNA, is synthesized in other neurons in the abdominal ganglion and is also bioactive. The R15α1 and R15α2 peptides were found to exert many similar actions on the cardiovascular, digestive, respiratory, and reproductive systems. However, the differences between many of the pharmacological effects of the R15α1 and R15α2 peptides indicate that alternative splicing in this system results in two functionally different peptides. Widespread immunoreactivity was found for an antibody directed against the R15α2 peptide, both in the central nervous system and the periphery. But because of the shared sequence with the R15α1 peptide, the antibody cross-reacts with the R15α1 peptide. To distinguish immunocytochemically between the two peptides, we also raised a second antibody that recognizes only the R15α1 peptide. This antibody labeled the cell body of only one neuron in the central nervous system, R15, although widespread immunoreactivity was found in axons and varicosities in the periphery.