title: Use of antagonists to define tachykininergic control of intestinal motility in pigs.
abstract: 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.
authors.affiliation: Institute of Medical Physiology, Panum Institute, National University Hospital, University of Copenhagen, Denmark.
authors.forename: P T
authors.initials: PT
authors.lastname: Schmidt
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: 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*
chemical_list: D015320:Tachykinins; D013373:Substance P; D018738:Hexamethonium; D001285:Atropine; D015288:Neurokinin A; D002211:Capsaicin; D010646:Phentolamine