Use of antagonists to define tachykininergic control of intestinal motility in pigs.
The involvement of the tachykinins in extrinsic nervous control of motility was studied in isolated, vascularly perfused, porcine ileal segments. Substance P and neurokinin A (10(-8) M) stimulated motility, and nonpeptide NK1 and NK2 receptor antagonists (10(-6) M) abolished this. Electrical stimulation of the mixed extrinsic nerves (8 Hz) had no effect alone or with atropine (10(-6) M) or phentolamine (10(-5) M), but increased motility during coinfusion of both blockers. This effect was abolished by hexamethonium (3 x 10(-5) M), and was reduced by over 80% by the NK1 receptor antagonist. As previously shown, substance P and neurokinin A were released during nerve stimulation, only during blockade of alpha-adrenergic and muscarinic receptors, and the release was abolished by hexamethonium. Capsaicin infusions (10(-5) M) increased substance P and neurokinin A release, and weakly stimulated small intestinal motility, but this was not inhibited by the tachykinin antagonists. Our results suggest that intrinsic tachykinin-producing neurons, controlled by extrinsic, nicotinic, excitatory neural pathways, and extrinsic adrenergic, inhibitory pathways, participate in the regulation of small intestinal motility.
Schmidt
P T
PT
Institute of Medical Physiology, Panum Institute, National University Hospital, University of Copenhagen, Denmark.
Holst
J J
JJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D015288:Neurokinin A / Q000494:pharmacology; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D015320:Tachykinins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
D015320:Tachykinins; D013373:Substance P; D018738:Hexamethonium; D001285:Atropine; D015288:Neurokinin A; D002211:Capsaicin; D010646:Phentolamine