A novel motility effect of tachykinins in normal and inflamed colon
Tsukamoto, M.; Sarna, S.K.; Condon, R.E.
American Journal of Physiology 272(6 Pt 1): G1607-G1614
1997
ISSN/ISBN: 0002-9513 PMID: 9227499 Document Number: 476306
The role of tachykinins in stimulating phasic and giant migrating contractions (GMCs) in the normal and inflamed colon in conscious dogs was investigated by close-intra-arterial infusions of test substances. At low doses (0.1 nmol), substance P and neurokinin (NK-1) receptor agonist ((Sar-9,Met(O-2)-11)substance P) stimulated phasic contractions only. At higher doses (2.0 nmol), they stimulated phasic contractions and GMCs. The phasic contractions were blocked partially but significantly by prior close-intra-arterial infusions of tetrodotoxin and atropine but not by hexamethonium. NK-1 receptor antagonist partially but significantly inhibited the phasic contractile response to substance P, whereas NK-2 and NK-3 receptor antagonists had no significant effect. The contractile response to NK-2 receptor agonist was less than one-half of the response to substance P; NK-3 receptor agonist did not stimulate any contractile activity. The stimulation of GMCs by higher doses of substance P was not blocked by prior infusions of atropine, tetrodotoxin, or NK-1, NK-2, and NK-3 receptor antagonists, nor was the contractile response to substance P blocked by H-1 and H-2 receptor antagonists. Inflammation depressed the phasic contractile response but enhanced the stimulation of GMCs by substance P. The ability of substance P to stimulate GMCs is novel and suggests its potential role in increasing the frequency of these contractions during colonic inflammation.