Source: Annual Congress 2002 - Bronchial responsiveness in asthma and COPD
Disease area: Airway diseases

Abstract

Cyclic ADP-ribose(cADO-R) is an endogeous metabolite of nicotinamide adenine dinucleotide(NAD), and it has recently been repotedd that inhibition of cADP-R produces vasodilation of bovine coronary arteries (Hypertension 35; 397, 2000), indicating a putative role of cADP-R in vascular smooth muscle contraction. In the present study, to elucidate the effect of cADP-R on airway smooth muscle contractile responses and its mechanism of action, we studied canine bronchial segments under isometric conditions in vitro in the presence of indomethacin to prevent the release of cycloxygenase products. Addition of nicotinamide(0.1~10mM), a specific inhibition of ADP-ribosylcyclase, did not alter the resting tension, but attenuated the contractile responses to electrical field stimulation (EFS, 10Hz) and exgenously administered acetylcholine (10^-5 M) by 38.6% and 33.6%, respectively. These inhibitory effects of nicotinamide was significantly attenuated in the presence of 8-bromo cADP-R, a cADP-R antagonist or ryanodine, a inhibitor of Ca²⁺-induced Ca²⁺ release throughout the experiment. In contrast, pretreatment of tissues with thapsigargin or verapamil did not alter the nicotinamide-induced inhibition of the contractile responses. These results suggest that cADP-R may play a role in muscarinic receptor-mediated contraction of airway smooth muscle cells probably by acting on the Ca²⁺ release from ryanodine-sensitive Ca²⁺ store. (supposed in part by Grant No. 12770305 from the Ministry of Education, Science and Culture, Japan)

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Citations should be made in the following way:
E. Tagaya, J. Tamaoki, M. Kondo, K. Isono, K. Kawatani, M. Taira, A. Nagai (Tokyo, Japan). Effect of cyclic ADP-ribose on canine airway smooth muscle contraction. Eur Respir J 2002; 20: Suppl. 38, 1211

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