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Differences in circular muscle contraction and peristaltic motor inhibition caused by tachykinin NK 1 receptor agonists in the guinea‐pig small intestine
Author(s) -
Shahbazian,
Peter Holzer
Publication year - 2000
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 - 10.1046/j.1365-2982.2000.00199.x
Subject(s) - peristalsis , agonist , receptor , medicine , tachykinin receptor , endocrinology , chemistry , muscle contraction , inhibitory postsynaptic potential , biology , substance p , neuropeptide
The tachykinin NK 1 receptor agonist substance P methyl ester (SPOME) impedes intestinal peristalsis by releasing nitric oxide (NO) from inhibitory motor neurones. Since NK 1 receptor agonists differ in their receptor interaction, we set out to compare a range of NK 1 receptor agonists including SPOME, septide and GR‐73 632 in their effects on propulsive peristalsis and circular muscle activity in the guinea‐pig isolated small intestine. SPOME (100–300 n M ) inhibited peristalsis by a rise of the pressure threshold at which peristaltic waves were triggered, whereas septide and GR‐73 632 (30–300 n M ) interrupted peristalsis by causing circular muscle spasms. Separate experiments showed that all three NK 1 receptor agonists caused contraction of the circular muscle, which was enhanced by the NO synthase inhibitor N G ‐nitro‐ L ‐arginine methyl ester (300 μ M ) and the P2X purinoceptor antagonist suramin (300 μ M ). In contrast, tetrodotoxin (300 n M ) augmented the contractile effect of septide and GR‐73 632 but not that of SPOME. It is concluded that the motor response to NK 1 receptor agonists involves release of NO and adenosine triphosphate from inhibitory motor neurones. However, the NK 1 receptor agonists differ in the mechanism by which they cause inhibitory transmitter release, which corresponds to differences in their antiperistaltic action.