Contractile responses to natural tachykinins and selective tachykinin analogs in normal and inflamed ileal and colonic muscle.
BACKGROUND
Tachykinins and acetylcholine are main physiological motility stimulators in the gut by their effects exerted through neurokinin and muscarinic receptors.


METHODS
Longitudinal and circular muscle strips from normal ileum and colon or corresponding tissues from patients with inflammatory bowel disease were studied in organ baths. Contractile responses to the tachykinins substance P, neurokinin A, neurokinin B and neuropeptide gamma and specific analogs for their respective receptors were compared to acetylcholine.


RESULTS
Acetylcholine caused concentration-dependent phasic contractions in longitudinal and circular muscle of normal ileum and colon (both P < 0.01). In inflamed tissues, contractile responses were reduced to 17%-33% in ileum (P < 0.05) and 3%-26% in colon (P < 0.01). Both natural tachykinins and their specific analogs caused concentration-dependent phasic, tonic and rhythmic contractions (each P < 0.01). Neuropeptide gamma was most potent in contracting the ileum and colon, followed by neurokinin A, substance P and neurokinin B, let alone longitudinal muscle of the ileum where neuropeptide gamma and neurokinin A were equipotent. Of the tachykinin analogs, Nle10-NKA(4-10) was more potent than substance P methyl ester and senktide, indicating neurokinin 2 receptors are predominant for contractile effects of tachykinins. In inflamed tissues, contractile responses to tachykinins were reduced to 0%-42% in ileum (P < 0.05) and 0%-17% in colon (P < 0.01) compared to controls.


CONCLUSIONS
In humans, tachykinins exert gut contractile effects, of similar strength as acetylcholine, predominantly through activation of neurokinin 2 receptors. These responses are greatly reduced in inflamed tissues of ulcerative colitis and Crohn disease.
Al-Saffar
A
A
Dept. of Pharmacology, AstraZeneca, Boston, USA.
Hellström
P M
PM
D000109:Acetylcholine / Q000502:physiology; D003093:Colitis, Ulcerative / Q000503:physiopathology*; D003106:Colon / Q000503:physiopathology*; D003424:Crohn Disease / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology; D006801:Humans; D007082:Ileum / Q000503:physiopathology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000502:physiology*; D018039:Receptors, Tachykinin / Q000502:physiology; D012016:Reference Values; D015320:Tachykinins / Q000819:agonists* / Q000502:physiology*
D018039:Receptors, Tachykinin; D015320:Tachykinins; D000109:Acetylcholine