Mechanisms of excitatory actions of neurotensin on canine small intestinal circular muscle in vivo and in vitro.
We have shown previously that close intra-arterial injections of neurotensin in vivo inhibited phasic activity induced by field stimulation of the canine small intestine during anaesthesia but had little effect during quiescence. In contrast, in vitro in the present study, full thickness strips of the muscularis externa cut in the circular axis responded to the lowest effective neurotensin concentrations (10(-12) to 10(-9) M) with an increase in frequency and amplitude of spontaneous contractions; as the concentration was increased from 10(-8) to 10(-7) M, neurotensin inhibited spontaneous activity. A small tonic contraction also occurred; it was maximal at 10(-7) M. Since sufficient tetrodotoxin to block field-stimulated nerve responses did not significantly reduce any of these responses in vitro, the neurotensin responses in vitro did not appear to involve actions on nerves. Indomethacin did not alter the excitatory response to 10(-11) M neurotensin but 5,8,11,14-eicosatetraynoic acid inhibited the excitatory response in a reversible fashion, without altering the response to acetylcholine. Thus excitation in vitro may require the release of excitatory metabolites of arachidonic acid via the lipoxygenase pathway. The neurotensin response in vivo was further studied by evaluating its actions against repetitive submaximal contractions induced by intra-arterial injections of acetylcholine given every minute. Doses that produced a short inhibition of the field-stimulated activity (10(-11) to 10(-10) mol intra-arterially) did not produce inhibition but 10(-10) mol significantly increased the response to acetylcholine. Higher doses (10(-9) mol) produced a significant inhibition of the first subsequent acetylcholine dose but no enhancement of later doses.(ABSTRACT TRUNCATED AT 250 WORDS)
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009496:Neurotensin / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015117:5,8,11,14-Eicosatetraynoic Acid; D009496:Neurotensin; D013779:Tetrodotoxin; D004533:Egtazic Acid; D000109:Acetylcholine