A novel motility effect of tachykinins in normal and inflamed colon

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 (NK₁) receptor agonist |[Sar⁹,Met(O₂)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. NK₁ receptor antagonist partially but significantly inhibited the phasic contractile response to substance P, whereas NK₂ and NK₃ receptor antagonists had no significant effect. The contractile response to NK₂ receptor agonist was less than one-half of the response to substance P; NK₃ 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 NK₁, NK₂, and NK₃ receptor antagonists, nor was the contractile response to substance P blocked by H₁ and H₂ 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.