F. Marino, M. Cosentino, F. De Ponti, C. Giaroni, L. Somaini, R. Bombelli, M. Ferrari, A.J. Aasen, S. Lecchini, G. Frigo
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引用次数: 6
Abstract
1 The present study examined the role of muscarinic receptors in the modulation of noradrenaline (NA) release in the guinea-pig isolated distal colon. The spontaneous endogenous NA overflow assayed by HPLC-ED was taken as an index of NA release from enteric noradrenergic nerve terminals.
2 Physostigmine (10 μm) significantly enhanced spontaneous endogenous NA overflow. Hyoscine (muscarinic antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M1-selective antagonists), and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116, M2-selective antagonist) inhibited NA overflow in a concentration dependent manner, with the following EC50 values: 131.74 (18.19–953.96), 101.62 (58.83–175.60), 150 (60–330), 30 (5–170) nm, respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M1- and M3- selective antagonist) had no significant effect up to 100 μm.
3 The muscarinic agonist oxotremorine inhibited NA overflow in a concentration dependent manner, with an EC50 value of 0.67 (0.30–1.51) μm. The response to oxotremorine was inhibited by muscarinic antagonists with the following order of potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine > 4-DAMP >> AF-DX 116.
4 In the presence of 3 μm tetrodotoxin (TTX), the effect of oxotremorine and 4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF-DX 116, instead of inhibiting, significantly enhanced NA overflow.
5 The present results indicate that, in the guinea-pig colon, endogenous acetylcholine sustains spontaneous NA release by activating muscarinic receptors possibly located on interneurones. In addition, inhibitory muscarinic receptors may exist on adrenergic terminals.