Variable α2-adrenoceptor-mediated inhibition of bronchoconstriction and peptide release upon activation of pulmonary afferents

Abstract

In the present study, we evaluated the possible regulation by α 2-receptor agonists (SKF 35886 and UK 14304) of peptide release and functional responses upon sensory nerve activation in the guinea-pig lung. The peptide release and bronchoconstriction caused by antidromic vagal nerve stimulation (low frequency, 1 Hz), and a low concentration of capsaicin (10 −8 M) and resiniferatoxin (3 × 10 −10 M) were attenuated by α 2-adrenoceptor agonists. The effects of capsaicin and nicotine in high concentrations and high frequency nerve stimulation (10 Hz) were influenced to a much smaller extent by α 2-adrenoceptor stimulation. The calcitonin gene-related peptide release evoked by bradykinin but not the functional effects was inhibited by α 2-adrenoceptor activation. It is concluded that α 2-adrenoceptor stimulation mainly inhibits the release of mediator and/or the bronchoconstriction caused by moderate activation of sensory nerves. It is necessary to measure mediator release directly to reveal prejunctional effects and not to rely only on indirect functional evidence.