Peptides in the nervous systems of cnidarians: structure, function, and biosynthesis.

Cnidarians are the lowest animal group having a nervous system and it was probably within this phylum or in a related ancestor group that nervous systems first evolved. The primitive nervous systems of cnidarians are strongly peptidergic. From a single sea anemone species, Anthopleura elegantissima, 17 different neuropeptides have been isolated so far, and we expect that many more neuropeptides (more than 30) must be present. All peptides are localized in neurons of cnidarians and we have demonstrated the presence of some of the peptides in neurosecretory dense-cored vesicles. Most neuropeptides have an excitatory or inhibitory action on whole cnidarians, muscle preparations, and isolated muscle cells, suggesting that these peptides are neurotransmitters or neuromodulators. One neuropeptide induces metamorphosis in planula larvae to become a polyp. This shows that cnidarian neuropeptides also are involved in developmental processes, such as cell differentiation and pattern formation. We have cloned the preprohormones for most of the cnidarian neuropeptides. These preprohormones have a high copy number of the immature neuropeptide sequence, which can be up to 37 neuropeptide copies per precursor molecule. In addition to well-known, "classical" processing enzymes, novel prohormone processing enzymes must be present in cnidarian neurons. These include a processing enzyme hydrolyzing at the C-terminal sides of acidic (Asp and Glu) residues and a dipeptidyl aminopeptidase digesting at the C-terminal sides of N-terminally located X-Pro and X-Ala sequences. All this shows that the primitive nervous systems of cnidarians are already quite complex, and that neuropeptides play a central role in the physiology of these animals.

Crucial role of ecto-5'-nucleotidase in differentiation and survival of developing neural cells.

ATP, an important signalling substance in the central nervous system, is hydrolysed to adenosine via a surface-located enzyme cascade. The final hydrolysis step from AMP to adenosine is catalysed by 5'-nucleotidase, a GPI-anchored surface protein. 5'-Nucleotidase is transiently expressed on developing neurones. An antisense oligonucleotide that suppresses the synthesis of 5'-nucleotidase inhibits NGF-induced neurite formation and survival in PC12 cells and cultures of cerebellar granule cells. The inhibitory effect of the antisense oligonucleotide can be completely or partially relieved by addition of soluble 5'-nucleotidase or of nucleosides to the medium. Our results suggest that 5'-nucleotidase is essential for the differentiation and survival of neural cells and represents an important and critical step in the hydrolysis cascade of extracellular nucleotides.

[Primary malignant lymphoma in the appendix vermiformis]. / Primaert malignt lymfom i appendix vermiformis.

Primary gastrointestinal lymphoma (PGL) is a rare condition. A case story concerning a 17 year old boy is presented and discussed. The symptoms were fever and pain in the lower right quadrant of the abdomen, where a tender tumor was palpable. The tentative diagnosis was periappendicular abscess and the patient was treated with antibiotics. As the tumor persisted, a laparotomy with resection of the coecum was performed. Histologic diagnosis was malignant lymphoma originating in the appendix. There was no sign of dissemination in the abdomen. Postoperative treatment with chemotherapy and radiation was carried out. PGL in the appendix in young patients, almost entirely males, will as here often be of the Burkitt type. The histologic type of the tumor, the staging and the radicality at operation are important with regard to prognosis.

Isolation of

Using a radioimmunoassay against the C-terminal sequence Arg-Pro-NH2 (RPamide) we have isolated the neuropeptide

Isolation of Leu-Pro-Pro-Gly-Pro-Leu-Pro-Arg-Pro-NH2 (Antho-RPamide), an N-terminally protected, biologically active neuropeptide from sea anemones.

Using a radioimmunoassay against the C-terminal sequence Arg-Pro-NH2 (RPamide), we have isolated the peptide Leu-Pro-Pro-Gly-Pro-Leu-Pro-Arg-Pro-NH2 (Antho-RPamide) from an extract of the sea anemone Anthopleura elegantissima. Antho-RPamide is located in neurons of sea anemones. Application of low concentrations of Antho-RPamide to tentacle preparations of sea anemones strongly increased the frequency and duration of spontaneous contractions, suggesting that this peptide is involved in neurotransmission. Antho-RPamide has a free N-terminus, yet its X-Pro-Pro sequence makes it relatively resistant to degradation by nonspecific aminopeptidases. Thus, we have discovered another strategy by which sea anemones protect the N-termini of their bioactive neuropeptides.