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Synthetic substance P increased the frequency and amplitude of spontaneously occurring contractions of circular and longitudinal muscle strips from canine gastric antrum in vitro. In longitudinal muscle, ED50 values calculated for frequency and amplitude were 3.7 X 10(-9) M and 9.7 X 10(-7) M, respectively. The effect of substance P on frequency in both layers and on amplitude in the circular layer was myogenic and unrelated to receptors for acetylcholine, norepinephrine, serotonin, histamine, and enkephalins. In the longitudinal muscle the amplitude response was partially inhibited by tetrodotoxin, atropine, and hexamethonium. The effect on amplitude but not on frequency was dependent on extracellular calcium. When compared to other stimulants of antral muscle contraction, the biological potency of substance P was higher than that of acetylcholine but significantly lower than that of gastrin and bombesin. Two putative substance P antagonists ([D-Pro2,D-Phe7,D-Trp9]substance P and [D-Pro2, D-Trp7,9]substance P) did not block the response of longitudinal muscle to substance P. Only the chronotropic response to substance P showed consistent, prolonged desensitization. These findings suggest that the mechanisms mediating the response to substance P in the canine antrum are different from other reported tissues.
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