Christian Wechselberger

Bv8, a small protein from frog skin and its homologue from snake venom induce hyperalgesia in rats

From skin secretions of Bombina variegata and Bombina bombina, we isolated a small protein termed Bv8. The sequence of its 77 amino acids was established by peptide analysis and by cDNA cloning of the Bv8 precursor. Bv8 stimulates the contraction of the guinea-pig ileum at nanomolar concentrations. The contraction is not inhibited by a variety of antagonists. Injection of a few micrograms of Bv8 into the brain of rats elicits, as assessed by the tail-flick test and paw pressure threshold, a marked hyperalgesia which lasts for about 1 h. Bv8 is related to protein A, a component of the venom of the black mamba. After i.c.v. injection, protein A is even more active than Bv8 in inducing hyperalgesia.

The mammalian homologues of frog Bv8 are mainly expressed in spermatocytes.

Bv8, a protein from skin secretions of Bombina variegata, reacts with receptors present in mammalian brain and intestine (Mollay et al. (1999) Eur. J. Pharmacol. 374, 189–196). As deduced from cloned cDNAs, the murine and human Bv8 homologues have identical amino‐terminal sequences and also contain 10 cysteines. From mouse testes, two forms of Bv8 mRNA have been characterized, of which one contains an additional exon which codes for 21 mostly basic amino acids. The mouse Bv8 gene is most active in mid‐late pachytene spermatocytes. In mouse testes, Bv8 mRNA can first be detected at the end of the second week post partum.

The Brix domain protein family – a key to the ribosomal biogenesis pathway?

Six (one archaean and five eukaryotic) protein families have similar domain architecture that includes a central globular Brix domain, and optional N- and obligatory C-terminal segments, both with charged low-complexity regions. Biological data for some proteins in this superfamily suggest a role in ribosome biogenesis and rRNA binding.

A new opioid peptide predicted from cloned cDNAs from skin of Pachymedusa dacnicolor and Agalychnis annae

We have isolated a cDNA encoding a precursor of dermorphin from the skin of Pachymedusa dacnicolor. Besides four copies of this opioid peptide, the deduced sequence also contains the genetic information for a novel peptide Tyr‐Ile‐Phe‐His‐Leu‐Met‐Asp‐NH2. This differs from Met‐deltorphin by the presence of Ile at position 2. In a related precursor from the skin of Agalychnis annae, the sequence of this peptide is in the 3′‐untranslated region of the cloned cDNA. From earlier results we predict that in skin peptides the second residue is d‐allo‐Ile. We have synthesized this and related peptides with different d‐amino acids, and determined their δ agonist activity. The peptide with d‐nor‐Leu binds with high affinity to δ receptors, while that with d‐allo‐Ile is about 100 times less active.

Peptides Related to Cholecystokinin in Nonmammalian Vertebrates

The hormones gastrin and cholecystokinin (CCK) belong to the same family of mammalian peptides. Both were originally isolated from the gastrointestinal tract and subsequently shown to be present also in brain.’” Different forms of these peptides varying in size exist in these tissues, but these are liberated from their precursors by differential proteolysis (to be described). The two hormones have the same COOH-terminal pentapeptide sequence. The main difference is that gastrin contains a tyrosine residue six amino acids from the carboxyl end, whereas in CCK tyrosine is the seventh residue (FIG. 1). The tyrosine residues are invariably sulfated in the various forms of CCK, but they are only partially sulfated in gastrins. From amphibian skin, three peptides, termed caeruleins, have been isolated which belong to the same family,4vs and from the position of the sulfated tyrosine residue, these skin peptides are of the CCK type. It has been assumed that gastrin, CCK, and caerulein are derived from a common ancestor that was present early in the evolution of vertebrates. This review summarizes our current knowledge of nonmammalian members of this family, and their possible phylogeny is discussed.