Neurokinin3-receptors are linked to inositol phospholipid hydrolysis in the guinea-pig ileum longitudinal muscle-myenteric plexus preparation

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Abstract
1 Tachykinin-stimulated inositol phospholipid hydrolysis was examined in slices of longitudinal muscle from guinea-pig ileum. 2 Substance P, neurokinin A and neurokinin B induced a concentration-dependent accumulation of total [3H]-inositol phosphates in the presence of 12 mm lithium with similar maximal responses and EC50 values. 3 The selective NK1-receptor agonist, substance P methyl ester, and the selective NK3-receptor agonist succ-[Asp6, MePhe8]-SP(6–11) (senktide) also stimulated [3H]-inositol phosphate formation with maximum responses of 50.69 ± 0.96 and 45.64 ± 1.17% relative to 10 μm substance P, respectively. Substance P methyl ester was approximately equipotent with substance P, whereas senktide was approximately 100 times more potent. 4 When added together, maximally effective concentrations of substance P methyl ester and senktide gave responses that were fully additive. In contrast, responses to substance P and neurokinin B were not additive. 5 The stimulation of [3H]-inositol phosphate formation by substance P, neurokinin B and senktide was not affected by atropine (2 μm) or tetrodotoxin (TTX, 0.3 μm). 6 The contractile effect of senktide was inhibited completely by TTX and partially blocked by atropine. Contractions induced by substance P methyl ester were not changed in the presence of TTX or atropine. 7 [d-Pro4, d-Trp7,9,10]-SP(4–11) competitively antagonized the action of substance P methyl ester on inositol phospholipid hydrolysis and contraction, but had no significant effect on senktide-induced inositol phospholipid breakdown or contraction. 8 These results suggest that NK3-receptors in the guinea-pig ileum are coupled to inositol phospholipid hydrolysis.