No abstract

The brain histamine system has been implicated in regulation of sensorimotor gating deficits and in Gilles de la Tourette syndrome. Histamine also regulates alcohol reward and consumption via H3 receptor (H3R), possibly through an interaction with the brain dopaminergic system. Here, we identified the histaminergic mechanism of sensorimotor gating and the role of histamine H3R in the regulation of dopaminergic signaling. We found that H3R knockout mice displayed impaired prepulse inhibition (PPI), indicating deficiency in sensorimotor gating. Histamine H1 receptor knockout and histidine decarboxylase knockout mice had similar PPI as their controls. Dopaminergic drugs increased PPI of H3R knockout mice to the same level as in control mice, suggesting that changes in dopamine receptors might underlie deficient PPI response when H3R is lacking. Striatal dopamine D1 receptor mRNA level was lower, and D1 and D2 receptor-mediated activation of extracellular signalregulated kinase 1/2 was absent in the striatum of H3R knockout mice, suggesting that H3R is essential for the dopamine receptor-mediated signaling. In conclusion, these findings demonstrate that H3R is an important regulator of sensorimotor gating, and the lack of H3R significantly modifies striatal dopaminergic signaling. These data support the usefulness of H3R ligands in neuropsychiatric disorders with preattentional deficits and disturbances in dopaminergic signaling.

Calaguala, an extract from the fern Polypodium decumanum, has been used to treat psoriasis and related immunological disorders. In an effort to explain Calaguala's medicinal effects the inhibitory activity of the extract in two platelet activating factor (PAF) related models has been investigated. In the first model, PAF was used to induce release of the proteolytic enzyme elastase in human neutrophils. Calaguala inhibited this effect with an IC50 of 0.1 mg/ml. The known PAF antagonist ginkgolide BN 52021 was used as a positive control and had an IC50 of 0.034 mg/ml. In the second model the inhibition of biosynthesis of PAF in neutrophils using lyso-PAF and labeled acetyl-CoA was studied. Also in this assay Calaguala showed a dose-dependent activity, the IC50 being 0.2 mg/ml. Since recent findings have indicated that PAF might be involved in the pathogenesis of psoriasis, it is possible that the activity shown by Calaguala in these PAF assays may contribute to the clinical efficacy of the extract. The PAF induced exocytosis assay was further used to guide the fractionation of the crude extract. From the acetone supernatant the nucleoside adenosine was isolated as an active principle. Pure adenosine dose-dependently inhibited the exocytosis induced by PAF (IC50 = 0.024 micrograms/ml) but was inactive in the biosynthesis assay. Adenosine is most probably one of the bioactive compounds of Calaguala responsible for its therapeutic properties.

L.-0. Lindbom and W. RolfsenKabi Pharmacia AB, S-751 82 Uppsala, Sweden Calaguala, an extract from the fern Polypodium decumanum, has been used to treat psoriasis and other immunologically related disorders. In order to elucidate whether an immunosuppressive mechanism could explain the clinical effect, Calaguala was studied in a skin model of allograft rejection in mice. Calaguala significantly prolonged the allograft survival compared with untreated transplanted mice. The results indicate that Calaguala exerts an immunosuppressive effect which could explain at least partly, the positive clinical results on psoriasis.

Usnic acid is present in the cortex of all Ramalinu species to a greater or lesser extent and is considered to be responsible for their antibiotic activity (1). Ramalina hierrensis Krog. & Osth. (2) (Ramalinaceae Ag., Lecanorales Nannf.) was collected on ,Juniperus phoenicea L. (savin) at La Dehesa (El Sabinar, El Hierro) and various chromatographic and spectroscopic procedures (IR, mass, 1H-NMR, 13C-NMR, NOE) were applied to a ketone extract of this lichen, affording the following products with very diverse structures: two triterpenes, ursolic acid and iso-arborinol acetate (3); three sterols, j3-sitosterol, er