Identification of alpha 1L-adrenoceptor in mice and its abolition by alpha 1A-adrenoceptor gene knockout.

BACKGROUND AND PURPOSE: The alpha(1L)-adrenoceptor has pharmacological properties that distinguish it from three classical alpha(1)-adrenoceptors (alpha(1A), alpha(1B) and alpha(1D)). The purpose of this was to identify alpha(1L)-adrenoceptors in mice and to examine their relationship to classical alpha(1)-adrenoceptors. EXPERIMENTAL APPROACH: Radioligand binding and functional bioassay experiments were performed on the cerebral cortex, vas deferens and prostate of wild-type (WT) and alpha(1A)-, alpha(1B)- and alpha(1D)-adrenoceptor gene knockout (AKO, BKO and DKO) mice. KEY RESULTS: The radioligand [(3)H]-silodosin bound to intact segments of the cerebral cortex, vas deferens and prostate of WT, BKO and DKO but not of AKO mice. The binding sites were composed of two components with high and low affinities for prazosin or RS-17053, indicating the pharmacological profiles of alpha(1A)-adrenoceptors and alpha(1L)-adrenoceptors. In membrane preparations of WT mouse cortex, however, [(3)H]-silodosin bound to a single population of prazosin high-affinity sites, suggesting the presence of alpha(1A)-adrenoceptors alone. In contrast, [(3)H]-prazosin bound to two components having alpha(1A)-adrenoceptor and alpha(1B)-adrenoceptor profiles in intact segments of WT and DKO mouse cortices, but AKO mice lacked alpha(1A)-adrenoceptor profiles and BKO mice lacked alpha(1B)-adrenoceptor profiles. Noradrenaline produced contractions through alpha(1L)-adrenoceptors with low affinity for prazosin in the vas deferens and prostate of WT, BKO and DKO mice. However, the contractions were abolished or markedly attenuated in AKO mice. CONCLUSIONS AND IMPLICATIONS: alpha(1L)-Adrenoceptors were identified as binding and functional entities in WT, BKO and DKO mice but not in AKO mice, suggesting that the alpha(1L)-adrenoceptor is one phenotype derived from the alpha(1A)-adrenoceptor gene.

Antioxidant activity of medicinal herb Rhodococcum vitis-idaea on galactosamine-induced liver injury in rats.

Aim of the study was to evaluate in vivo antioxidant action of medicinal herb Rhodococcum vitis-idaea (Rh.v) on galactosamine (GalN)-induced rat liver toxicity. The results showed that the hepatotoxicity and oxidative stress induced by GalN (700 mg/kg, s.c.) after 24 h evidenced by an increase in serum alanine aminotransferase and glutathione (GSH) S-transferase activities, and lipid peroxidation in liver homogenate were significantly inhibited, when 10 times diluted Rh.v. extract (5 ml/kg, i.p.) was given to rats 12 and 1 h before GalN treatment demonstrating that the extract of Rh.v is a potent antioxidant and protective against GalN-induced hepatotoxicity. The main antioxidant compound of the herb water extract used in the experiment was determined as arbutin, which possess 8% of dry weight of the herb. The electron spin resonance (ESR) spectrometer analysis revealed that the arbutin isolated from Rh.v exhibited strong superoxide and hydroxyl radical scavenging ability.

Free radical scavenging action of medicinal herbs from Mongolia.

In the present study we evaluated the free radical scavenging action of some medicinal herbs growing in Mongolia. The aqueous extract of nine herbs Chamenerion angustifolium (Ch.ang), Equisetum arvense (Eq.arv), Gentiana decumbens (Gn.dec), Geranium pratense (Gr.pra), Lomatogonium carinthiacum (L.car), Nonea poulla (N.pl), Phodococcum vitis-idaea (Ph.v), Sphallerocarpus gracilis (Sph.gr), Stellera chamaejasme (St.cha) were used in the present experiment. The free radical scavenging action was determined in vitro and ex vivo by using electron spin resonance (ESR) spectrometer and chemiluminescence (CL) analyzer. The results showed that extracts of Ch.ang, Gn.dec, Gr.pra, L.car, N.pl, Ph.v, Sph.gr and St. cha possess strong scavenging action of 1,1-diphenyl-2-picrylhydrazyl, superoxide and hydroxyl radicals. On the other hand, the radical scavenging action of Eq.arv was low. Extracts of N.pl and Ph.v markedly inhibited the CL generated from rat liver microsomal cytochrome P450 system whereas the CL was moderately inhibited by Eq.arv, Gn.dec, Gr.pra, L.car and St.cha. The extracts of Ch.ang and Sph.gr did not decrease the CL generation. Ch.ang, Gr.pra, L.car, N.pl, Ph.v and St.cha also depressed reactive oxygen production from polymorphonuclear leukocytes stimulated by phorbol-12-myristate acetate ex vivo. Thus it was confirmed that the medicinal herbs from Mongolia possess high antioxidant potency in vitro and ex vivo.