NEUROTENSIN MODULATES CHOLINERGIC AND NONCHOLINERGIC NEUROTRANSMISSION IN GUINEA-PIG MAIN BRONCHI IN-VITRO

Guinea-pig main bronchi were stimulated transmurally in vitro by elect rical field stimulation in the presence of indomethacin 10(-6) M, prop ranolol 10(-6) M and phosphoramidon 10(-5) M. TWO contractile neurogen ic responses were successively observed, The second noncholinergic con traction was concentration dependently inhibited or abolished by neuro tensin whereas the first cholinergic contraction was only partially in hibited. SR 48692, a novel antagonist of neurotensin receptors, reduce d the inhibition induced by neurotensin (pK(B) = 9.75) whereas levocab astine, an antagonist of low-affinity neurotensin receptors, did not s ignificantly modify the inhibitory effects of neurotensin on both neur ally-mediated contractions. These results demonstrate that neurotensin exerts an inhibitory effect on neurotransmission in guinea-pig airway s. Furthermore, the present study shows that the newly developed neuro tensin receptors antagonist, SR 48692, is a potent inhibitor of the ne urotensin inhibitory effects on cholinergic and noncholinergic contrac tions induced by electrical field stimulation of the guinea-pig isolat ed main bronchus.