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(-5) 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 (pKB = 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.
Martin
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CA
Département de Pharmacologie, Faculté de Médecine Paris-Ouest, France.
Gully
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D
Naline
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Advenier
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects / Q000294:innervation*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D009496:Neurotensin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D010446:Peptide Fragments; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C061060:neurokinin A (4-10), Nle(10)-; C079087:SR 48692; D013373:Substance P; D009496:Neurotensin; D015288:Neurokinin A; D000109:Acetylcholine