A NOVEL MOTILITY EFFECT OF TACHYKININS IN NORMAL AND INFLAMED COLON

The role of tachykinins in stimulating phasic and giant migrating cont ractions (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 agoni st [[Sar(9),Met(O-2)(11)]substance P] stimulated phasic contractions o nly. At higher doses (2.0 nmol), they stimulated phasic contractions a nd GMCs. The phasic contractions were blocked partially but significan tly by prior close-intra-arterial infusions of tetrodotoxin and atropi ne but not by hexamethonium. NK1 receptor antagonist partially but sig nificantly inhibited the phasic contractile response to substance P, w hereas NK2 and NK3 receptor antagonists had no significant effect. The contractile response to NK2 receptor agonist was less than one-half o f the response to substance P; NK3 receptor agonist did not stimulate any contractile activity. The stimulation of GMCs by higher doses of s ubstance P was not blocked by prior infusions of atropine, tetrodotoxi n, or NK1, NK2, and NK3 receptor antagonists, nor was the contractile response to substance P blocked by H-1 and Hz receptor antagonists. In flammation depressed the phasic contractile response but enhanced the stimulation of GMCs by substance P. The ability of substance P to stim ulate GMCs is novel and suggests its potential role in increasing the frequency of these contractions during colonic inflammation.