No abstract

Parietaria judaica-induced AHR in immunized rabbits was shown to be inhibited by pre-treatment with capsaicin, an effect that is not related to an action on the associated pulmonary infiltration of eosinophils. The involvement of NK2 receptor stimulation in this phenomenon also suggests that NK2 receptor antagonists may be useful for investigating mechanisms of bronchopulmonary alterations in asthmatic patients.

1 Nociceptin/orphanin FQ (N/OFQ) is the endogenous peptide ligand for a specific G-protein coupled receptor, the N/OFQ peptide receptor (NOP). The N/OFQ-NOP receptor system has been reported to play an important role in pain, anxiety and appetite regulation. In airways, N/OFQ was found to inhibit the release of tachykinins and the bronchoconstriction and cough provoked by capsaicin. 2 Here we evaluated the effects of NOP receptor activation in bronchoconstriction and airway microvascular leakage induced by intraesophageal (i.oe.) hydrochloric acid (HCl) instillation in rabbits. We also tested the effects of NOP receptor activation in SP-induced plasma extravasation and bronchoconstriction. 3 In anesthetized New Zealand rabbits bronchopulmonary function (total lung resistance (R L ) and dynamic compliance (C dyn )) and airway microvascular leakage (extravasation of Evans blue dye) were evaluated. 4 Infusion of i.oe. HCl (1 N) led to a significant increase in bronchoconstriction and plasma extravasation in the main bronchi and trachea of rabbits pretreated with propranolol, atropine and phosphoramidon. 5 Bronchoconstriction and airway microvascular leakage were inhibited by N/OFQ (3-30 mg kg

1 In some asthmatics, muscarinic receptor antagonists are eective in limiting bronchoconstrictor response, suggesting an abnormal cholinergic drive in these subjects. There is a growing body of evidences indicating that cholinergic neurotransmission is also enhanced by endothelin-1 (ET-1) in rabbit bronchi, mouse trachea and in human isolated airway preparations. 2 We investigated the role of secondary mediators in ET-1 induced potentiation of cholinergic nerve-mediated contraction in human bronchi, in particular the possible role of neuropeptides in this phenomenon. 3 Bronchial tissues after endothelin treatment were exposed to a standard electrical ®eld stimulation (EFS) (30% of EFS 30Hz)-induced contraction. In addition, in some experiments, preparations were treated with a tachykinin NK 2 receptor antagonist and subsequently exposed to the same protocol. HPLC and RIA were performed on organ bath¯uid samples. Moreover, the human bronchi were used for the b-PPT (preprotachykinin) mRNA extraction and semiquantitative reverse transcription polymerase chain reaction (RT ± PCR), prior to and 30 ± 40 min following ET-1 challenge. 4 The selective tachykinin NK 2 receptor antagonist, SR48968, was eective to reduce ET-1 potentiation of EFS mediated contraction. HPLC or RIA showed signi®cant increased quantities of NKA in organ bath euents after EFS stimulation in bronchi pretreated with ET-1. Finally, b-PPT mRNA level after stimulation of bronchi with ET-1 was increased about 2 fold respect to control untreated bronchi. 5 In conclusion, this study demonstrated that, at least in part, the ET-1 potentiation of cholinergic nerve-mediated contraction is mediated by tachykinin release, suggesting that in addition to nerves, several type of cells, such as airway smooth muscle cell, may participate to neuropeptide production.