Characterization of neurokinin type 1 receptor in canine small intestinal muscle

The binding of [3H]substance P (SP) was localized and characterized in canine small intestine. The highest density of [3H]SP binding occurred in the fraction enriched in circular muscle membranes (Bmax 148 +/- 14 fmol/mg; Kd 0.81 +/- 0.01 nM). In the kinetics studies binding was reversible, yielding a similar Kd value. NK1 agonists and antagonists fully displaced, but ligands at the NK2 and NK3 receptor only partially displaced, [3H]SP binding. The potency order of displacement resembled that for the human NK1 receptor ortholog rather than the rat NK1 receptor. Densities of [3H]SP binding were lower in myenteric plexus and longitudinal muscle membrane fractions, but suggested binding in both neural and muscle membranes. The conclusion is that NK1 receptors occur primarily in canine intestine circular muscle plasma membrane.