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Identification of mechanisms for duodenal contraction induced by tachykinins in the rat
Author(s) -
KIM Y. C.,
HELLSTRÖM P. M.
Publication year - 1993
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.1993.tb00113.x
Subject(s) - neurokinin a , neurokinin b , tachykinin receptor , substance p , hexamethonium , medicine , endocrinology , receptor , chemistry , muscle contraction , acetylcholine , neuropeptide , biology , biochemistry
Mechanisms for contractile effects of tachykinins on muscle strips of rat duodenum were studied using substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and neuropeptide K (NPK), and the tachykinin analogues SP methyl ester (SPME), Nle 10 ‐NKA(4–10) (NleNKA) and senktide (SENK) selective for neurokinin (NK)‐1, NK‐2 and NK‐3 receptors, respectively. NK receptors responsible for smooth muscle contraction were identified using selective ligands to protect NK receptors combined with inactivation of residual receptors with N‐ethylmaleimide. Tachykinins (10 −9 to 10 −5 M) caused dose‐related contractions of the muscle strips. The order of potency of native tachykinins was NKA > NKB > SP > NPK in circular, and NKB > NKA > NPK > SP in longitudinal muscle, whereas that of selective tachykinin analogues was SENK > NleNKA > SPME. NKA, NleNKA and SENK were equieffective as acetylcholine, whereas SP, SPME, NKB and NPK were less effective. Spantide decreased the sensitivity to all tachykinin analogues. Atropine reduced the sensitivity to SENK only, whereas hexamethonium reduced the sensitivity to SENK and SPME, but not to NleNKA. Selective receptor protection with SPME, NleNKA or SENK protected contractions induced by SPME, NleNKA and SENK, respectively. Responses to tachykinin analogues were reduced in Ca 2+ ‐free medium. Thus, NKA is suggested to be the dominating tachykinin to stimulate contraction of the rat duodenum via NK receptors coupled to Ca 2+ ‐dependent signal transduction pathways. Of the receptors available, the NK‐1 subtype involves a nicotinic transmission step, and the NK‐3 subtype also a muscarinic step, whereas the NK‐2 receptor subtype is not dependent on cholinergic mechanisms.