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Neurokinin 3 ‐receptors are linked to inositol phospholipid hydrolysis in the guinea‐pig ileum longitudinal muscle‐myenteric plexus preparation
Author(s) -
Guard S.,
Watling K.J.,
Watson S.P.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11509.x
Subject(s) - substance p , neurokinin a , endocrinology , neurokinin b , medicine , inositol , agonist , tachykinin receptor , chemistry , myenteric plexus , inositol phosphate , receptor , tetrodotoxin , neuropeptide , biology , biochemistry , immunohistochemistry
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 [ 3 H]‐inositol phosphates in the presence of 12 m m lithium with similar maximal responses and EC 50 values. 3 The selective NK 1 ‐receptor agonist, substance P methyl ester, and the selective NK 3 ‐receptor agonist succ‐[Asp 6 , MePhe 8 ]‐SP(6–11) (senktide) also stimulated [ 3 H]‐inositol phosphate formation with maximum responses of 50.69 ± 0.96 and 45.64 ± 1.17% relative to 10 μ m 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 [ 3 H]‐inositol phosphate formation by substance P, neurokinin B and senktide was not affected by atropine (2 μ m ) or tetrodotoxin (TTX, 0.3 μ m ). 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 ‐Pro 4 , d ‐Trp 7,9,10 ]‐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 NK 3 ‐receptors in the guinea‐pig ileum are coupled to inositol phospholipid hydrolysis.