Histidine-rich basic peptide: a cardioactive neuropeptide from Aplysia neurons R3-14

J. T. Campanelli and R. H. Scheller We have previously demonstrated that neurons R3-14 of the Aplysia abdominal ganglia specifically express a gene encoding a 108-amino acid neuropeptide precursor. This precursor is postranslationally processed by cleavage of a signal sequence and two internal dibasic residues resulting in three peptides. The peptide products are colocalized in dense core granules throughout the R3-14 processes that innervate the efferent vein of the gill and the auricle. Gel filtration and reverse phase high-pressure liquid chromatography (rpHPLC) were used to purify a 4.9-kDa peptide produced by the R3-14 neurons. We call this peptide the histidine-rich basic peptide (HRBP), which reflects its primary structure. In vitro tension measurements of cannulated Aplysia hearts revealed dose-dependent cardioexcitatory actions of HRBP. HRBP increased both beat frequency and amplitude with a threshold of 10(-7) M. HRBP increased the amplitude of ventricular contractions in a dose-dependent manner, whereas the frequency of contraction is unaffected. In contrast both the amplitude and frequency of auricular contractions were enhanced. High concentrations of HRBP also had a positive tonotropic effect on the auricle. HRBP was also demonstrated to have actions on tissue of the gut. Circular muscles of the crop adjacent to the anterior gizzard showed infrequent spontaneous contractions. Both HRBP and acetylcholine (ACh) induced repetitive contractions of this muscle. Circular muscles of the posterior gizzard had a high degree of spontaneous activity when continually perfused. Contraction amplitude and frequency was increased by HRBP and ACh, whereas contractility was inhibited by Phe-Met-Arg-Phe-amide (FMRFamide).