The β-adrenoceptor antagonist propranolol induced Ca2+ mobilisation and enhanced contractile responses in guinea pig airways, in vitro
S. E. V. Albinsson, M. K. L. Grenegård, E. G. Lindström (Linköping, Sweden)
Source: Annual Congress 2002 - Bronchial responsiveness in asthma and COPD
Session: Bronchial responsiveness in asthma and COPD
Session type: Poster Discussion
Number: 1207
Disease area: Airway diseases
Abstract It is well known that the β-adrenoceptor antagonist propranolol can induce airway obstruction in asthmatic patients. Propranolol has been shown to increase the sensitivity of airways to several contractile agents, both in vivo and in vitro . Initially, this potentiation was attributed to the β-adrenoceptor blocking effect of propranolol but recent studies indicate that other mechanisms are involved. The aim of this study was to further examine the mechanism behind the effects of propranolol on guinea pig airways, in vitro . Airway responsiveness to ovalbumin was determined in sensitised tracheal ring preparations 1h after propranolol treatment. Capsaicin treatment was used to evaluate a possible role of sensory neuropeptides in the responses. Cytosolic calcium transients in both adherent cells and cells in suspension were measured using a fura-2AM technique. In the preparations propranolol (10-6 M) had no intrinsic effect, but significantly augmented the contractile response to ovalbumin with 70 % (p<0.01). Depletion of sensory nerves with capsaicin reduced the effect of propranolol. In ASM cells propranolol directly induced distinct calcium responses in several experiments. However, incubation with propranolol (10-5 M) did not alter the subsequent calcium response to bradykinin (10-9 M). These results indicate that propranolol enhance the hyperreactivity to ovalbumin in sensitised guinea pig airways in vitro . This effect was in part mediated by neuropeptides from sensory nerves. We also conclude that propranolol, by unknown mechanisms, is able to cause calcium transients in smooth muscle cells and could therefore directly influence ASM cell activity.
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S. E. V. Albinsson, M. K. L. Grenegård, E. G. Lindström (Linköping, Sweden). The β-adrenoceptor antagonist propranolol induced Ca2+ mobilisation and enhanced contractile responses in guinea pig airways, in vitro . Eur Respir J 2002; 20: Suppl. 38, 1207
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