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Ca2+ dependency of the release of nitric-oxide from nonadrenergic noncholinergic nerves
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Author
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Abstract
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1 The role of Ca2+ in nitrergic neurotransmission was studied in the canine ileocolonic junction. 2 The specific N-type voltage-sensitive Ca2+ channel blocker omega-conotoxin GVIA (CTX, 10 - 100 nm) significantly reduced the electrically-evoked (2-16 Hz, 1-2 ms pulse width) non-adrenergic non-cholinergic (NANC) relaxations, preferentially affecting those to low frequency stimulation, in circular muscle strips of the ileocolonic junction. In contrast, the nerve-mediated NANC-relaxations in response to acetylcholine (30 muM), gamma-aminobutyric acid (100 muM) and adenosine 5'-triphosphate (100 muM), as well as the relaxations to nitric oxide (NO) (3 - 10 muM) and nitroglycerin (1 muM), remained unaffected. 3 A NO-related substance (NO-R), released from the ileocolonic junction in response to NANC nerve stimulation (4 and 16 Hz, 2 ms pulse width), was assayed with a superfusion bioassay cascade. CTX (50 nm) reduced the release of NO-R induced by electrical impulses (4 Hz: from 18 +/- 4% to 6 +/- 4%; 16 Hz: from 33 +/- 2% to 14 +/- 4%, n = 5), but not that in response to the nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 0.3 mm). In Ca2+-free medium, the release of NO-R evoked by electrical impulses or DMPP was inhibited. The L-type Ca2+ channel blockers verapamil (1 - 3 muM) and nifedipine (1 muM) had no effect. 4 From these results we conclude that the release of NO-R in response to NANC nerve stimulation is Ca2+-dependent. The electrically-evoked release of NO-R results from Ca2+ entry through CTX-sensitive N-type voltage-sensitive Ca2+ channels, whereas that induced by nicotinic receptor activation involves CTX-insensitive Ca2+ channels, different from the L- or N-type. |
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Language
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English
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Source (journal)
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British journal of pharmacology. - London
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Publication
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London
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1993
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ISSN
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0007-1188
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DOI
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10.1111/J.1476-5381.1993.TB13964.X
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Volume/pages
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110
:4
, p. 1329-1334
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ISI
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A1993MJ19300012
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Full text (Publisher's DOI)
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