No abstract

1 The e ect of endogenous glucocorticoid hormones on the expression of rat B 1 receptors was examined by means of molecular and pharmacological functional approaches. 2 Rats were adrenalectomized (ADX), and 7 days after this procedure the intradermal injection of B 1 receptor agonist des-Arg 9 -BK produced a signi®cant increase in the paw volume, while only a weak e ect was observed in sham-operated animals. A similar increase in the contractile responses mediated by B 1 agonist des-Arg 9 -BK was also observed in the rat portal vein in vitro.3 Chemical ADX performed with mitotane (a drug that reduces corticosteroid synthesis) produced essentially the same up-regulation of B 1 receptors as that observed in ADX rats. 4 The modulation of B 1 receptor expression was evaluated by ribonuclease protection assay, employing mRNA obtained from the lungs and paw of ADX rats. 5 Additionally, both paw oedema and contraction of portal vein mediated by B 1 agonist des-Arg 9 -BK in ADX rats, were markedly inhibited by treatment with dexamethasone, or COX-2 inhibitor meloxican, or with the NF-kB inhibitor PDTC. Interestingly, the same degree of inhibition was achieved when the animals were treated with a combination of submaximal doses of dexamethasone and PDTC. 6 The involvement of NF-kB pathway was further con®rmed by mobility shift assay using nuclear extracts from lung, paw and heart of ADX rats. It was also con®rmed that the treatment of ADX rats with dexamethasone, PDTC or dexamethasone plus PDTC completely inhibit NF-kB activation caused by absence of endogenous glucucorticoid. 7 Together, the results of the present study provide, for the ®rst time, molecular and pharmacological evidence showing that B 1 kinin receptor expression can be regulated through endogenous glucocorticoids by a mechanism dependent on NF-kB pathway. Clinical signi®cance of the present ®ndings stem from evidence showing the importance of B 1 kinin receptors in the mediation of in¯ammatory and pain related responses.

These results confirm and extend our previous studies, and demonstrate the clear oral anti-inflammatory and anti-allergic properties of the active principle(s) present in the barks of D. winteri, thus confirming its reported medicinal use in folk medicine for the management of airway diseases.

Cultures of retinal pigment epithelium are suitable and sensitive models to study cell damage and may contribute to unravelling the pathogenetic mechanisms of retinal degeneration.