Neurotensin modulates cholinergic and noncholinergic neurotransmission in guinea-pig main bronchi in vitro

Guinea-pig main bronchi were stimulated transmurally in vitro by electrical field stimulation in the presence of indomethacin 10 −6 M, propranolol 10 −6 M and phosphoramidon 10 −6 M. Two contractile neurogenic responses were successively observed. The second noncholinergic contraction was concentration dependently inhibited or abolished by neurotensin whereas the first cholinergic contraction was only partially inhibited. SR 48692, a novel antagonist of neurotensin receptors, reduced the inhibition induced by neurotensin (pK B = 9.75) whereas levocabastine, an antagonist of low-affinity neurotensin receptors, did not significantly modify the inhibitory effects of neurotensin on both neurally-mediated contractions. These results demonstrate that neurotensin exerts an inhibitory effect on neurotransmission in guinea-pig airways. Furthermore, the present study shows that the newly developed neurotensin receptors antagonist, SR 48692, is a potent inhibitor of the neurotensin inhibitory effects on cholinergic and noncholinergic contractions induced by electrical field stimulation of the guinea-pig isolated main bronchus.