Synergism between fluoxetine and the mGlu2/3 receptor agonist, LY379268, in an in vitro model for antidepressant drug-induced neurogenesis.

We examined the interaction between the selective serotonin reuptake inhibitor, fluoxetine, and group-II metabotropic glutamate (mGlu) receptors using progenitor cells isolated from cultured cerebellar granule cells, considered as an in vitro model of antidepressant-drug induced neurogenesis. These cells expressed mGlu3 receptors negatively coupled to adenylyl cyclase. A 72-h treatment with either fluoxetine or low concentrations of mGlu2/3 receptor agonists (LY379268 or 2R,4R-APDC) enhanced cell proliferation. The action of fluoxetine was mediated by the activation of 5-HT(1A) receptors. We found a strong synergism between fluoxetine and LY379268 in enhancing cell proliferation and inhibiting cAMP formation. The increased cell proliferation induced by fluoxetine+LY379268 was abrogated by the cAMP analogue, 8-Br-cAMP, as well as by drugs that inhibit the mitogen-activated protein kinase and phosphatidyilinositol-3-kinase pathways. Interestingly, fluoxetine and LY379268 also acted synergistically in promoting neuronal differentiation when progenitor cells were incubated in the presence of serum. These data support the hypothesis that a combination between classical antidepressants and mGlu2/3 receptor agonists may be helpful in the experimental treatment of depression.

A family of bombinin-related peptides from the skin of Bombina variegata.

A peptide fraction was isolated from the skin of Bombina variegata that showed antimicrobial activity. This fraction contained several molecular species, all of them consisting of 27 amino acid residues, with a constant C-terminal region (from residues 14-27), including an amidated carboxyl end and a variable N-terminal segment. These peptides are related but not identical to bombinin [Csordas, A. & Michl, H. (1970) Monatsh. Chem. 101, 182-189]. By using synthetic oligonucleotides corresponding to the C-terminal region of the peptides, a cDNA library from the skin of B. variegata was screened and several positive clones coding for the corresponding peptide precursors were isolated and sequenced. Each clone contained the genetic information for a different bombinin-like peptide. The antimicrobial activity towards different bacterial species of a synthetic peptide corresponding to one of the variants deduced from cDNA sequences was tested. This peptide was found to be mainly active against different isolates of Staphylococci and Escherichia coli.

Effects of sauvagine, urotensin I and CRF on food intake in rats.

Sauvagine (SV) is a forty amino acid peptide, isolated from the skin of the South American frog Phyllomedusa sauvagei and structurally related to fish Urotensin I (U1) and to mammalian corticotropin releasing factor (CRF). Intracerebroventricular (ICV) injections of SV (0.3-2.0 micrograms/rat), CRF (1.0-15.0 micrograms/rat) and U1 (0.5-2.0 micrograms/rat) inhibited feeding in 18 hr food deprived rats. By subcutaneous (SC) route, only SV (3.0-10.0 micrograms/kg) and U1 (10.0-20.0 micrograms/kg) exhibited anorexogenic effects, CRF being completely inactive up to a dose of 200 micrograms/kg. Vagotomy did not prevent the feeding inhibition by SC SV. In ICV injected rats, CRF increased grooming in comparison with both food deprived and satiated controls, while SV and U1 increased grooming only in comparison with fasted controls. Compared to satiated animals, food deprived rats when injected ICV with anorexogenic doses of the peptides showed decreased resting and increased moving. Rats given SC injections of SV and U1 significantly decreased grooming in comparison with both food deprived and satiated controls, while increased resting only in comparison with fasted controls. CRF by the SC route did not affect the behaviour of the rat.