Human isolated ileum: motor responses of the circular muscle to electrical field stimulation and exogenous neuropeptides

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Abstract
(1) Circularly-oriented muscle strips from the human ileum responded to electrical field stimulation (1–50 Hz) with frequency-related primary relaxation at low frequency and primary contractions at high frequencies of stimulation. Both responses were abolished or markedly reduced by tetrodotoxin (1 μM). (2) Atropine (3 μ M) or omega conotoxin (0.1 μM) reduced but dit not abolish contraction to electrical field stimulation and enhanced the relaxation. Omega conotoxin (0.1 μM) did not affect carbachol-induced contraction nor isoprenaline-induced relaxation. (3) Neurokinin A and substance P (1 nM-1 μM) produced a concentration-dependent contraction. The NK-1 receptor selective agonist, [Pro9]SP sulfone and the NK-2 receptor selective agonist [βAla8]NKA(4-10) prodneed a contraction superimposable to that of substance P and neurokinin A, respectively. On the other hand, [MePhe7]-neurokinin B, an NK-3 receptor selective agonist was ineffective up to 1 [M. The response to substance P or neurokinin A was unaffected by atropine (3 μM). (4) Galanin, up to 0.1 μM produced a weak and inconsistent contraction. (5) Vasoactive intestinal polypeptide (10 nM - 1 μM) produced a concentration-dependent relaxation while human alpha calcitonin gene-related peptide exerted a weak and inconsistent relaxant effect. (6) These findings indicate that both cholinergic excitatory and non-cholinergic inhibitory nerves affect the motility of the circular muscle of the human small intestine. Transmitter release from excitatory nerves seems largely mediated by activation of omega conotoxin-sensitive (N-type) calcium channels. Tachykinins exert a potent contractile effect independently of cholinergic nerves via NK-1 and NK-2 receptors.