Tachykinin activation of muscarinic inhibition in canine small intestine is SPP in nature.

Substance P when injected intraarterially into the small intestine of the anaesthetized dog during phasic activity produces three concentration dependent responses of the circular muscle. At lowest doses (approximately 10(-12) moles) inhibition occurs via release of acetylcholine to a muscarinic auto-receptor. At slightly higher doses (10(-10) moles) inhibition is preceeded by excitation via release of acetylcholine to muscarinic receptors on the smooth muscle. At still higher doses (10(-9) moles) substance P excites the smooth muscle directly. The present study demonstrates that other members of the tachykinin family also produce inhibition in vivo. The potency sequence was found to be physalaemin greater than or equal to substance P = neuromedin K greater than kassinin greater than alpha neurokinin = eledoisin. Such a sequence suggests that substance P is a natural stimulant of this pathway and that the receptor is SPP-like. The C-terminal fragment, substance P8-11, was a weak agonist at this receptor, while substance P1-9 was ineffective.