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Research ArticleArticle

N-Type Ca2+ Channels Trigger Release of Excitatory and Inhibitory Neurotransmitter from Nerve Endings in Canine Bronchi

Amer M. Johri and Luke J. Janssen
Journal of Pharmacology and Experimental Therapeutics August 1999, 290 (2) 847-853;
Amer M. Johri
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Luke J. Janssen
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Abstract

We set out to characterize the types of Ca2+ channels that mediate release of the predominant excitatory (acetylcholine) and inhibitory (norepinephrine) neurotransmitters in canine bronchi, using electrically evoked contractions and relaxations, respectively, as indicators of this release. We found that the selective N-type Ca2+ channel blocker (ω-conotoxin GVIA) eliminated electrically evoked contractions in a dose-dependent fashion (half-maximal inhibition in the presence of 1–5 nM) but had no significant effect on those evoked by exogenously added acetylcholine. Selective blockers of P-type Ca2+ channels (ω-agatoxin TK; 10−8 to 10−7 M) or ofl-type Ca2+ channels (nifedipine; 10−8 to 10−6 M) had no significant effect on the responses to neurally released or exogenously added acetylcholine. Likewise, electrically evoked relaxations were blocked by ω-conotoxin GVIA (10−7 M) but not by ω-agatoxin TK (10−7 M) or nifedipine (10−7 M); none of these Ca2+ channel blockers had a significant inhibitory effect on isoproterenol-triggered relaxations. We conclude that excitatory and inhibitory neurotransmission in canine bronchi is mediated predominantly by N-type Ca2+ channels, with little or no contribution from L-, P-, Q-, or T-type channels.

Footnotes

  • Send reprint requests to: Dr. L. J. Janssen, Department of Medicine, McMaster University (HSC-3U1), Hamilton, Ontario, Canada L8N 3Z5. E-mail: janssenl{at}fhs.csu.mcmaster.ca

  • ↵1 This work was supported by a grant from the Medical Research Council of Canada, a Career Award (to L.J.J.) from the Pharmaceutical Manufacturers’ Association of Canada (Health Research Foundation), and the Medical Research Council of Canada.

  • Abbreviations:
    ASM
    airway smooth muscle
    AgTX
    agatoxin TK
    ω-CTX
    ω-conotoxin GVIA
    EFS
    electrical field stimulation
    ACh
    acetylcholine
    S1
    S2, S3, first, second, and third series of electrical field stimulation pulse trains, respectively
    NE
    norepinephrine
    TTX
    tetrodotoxin
    • Received October 22, 1998.
    • Accepted April 28, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 290 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 290, Issue 2
1 Aug 1999
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Research ArticleArticle

N-Type Ca2+ Channels Trigger Release of Excitatory and Inhibitory Neurotransmitter from Nerve Endings in Canine Bronchi

Amer M. Johri and Luke J. Janssen
Journal of Pharmacology and Experimental Therapeutics August 1, 1999, 290 (2) 847-853;

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Research ArticleArticle

N-Type Ca2+ Channels Trigger Release of Excitatory and Inhibitory Neurotransmitter from Nerve Endings in Canine Bronchi

Amer M. Johri and Luke J. Janssen
Journal of Pharmacology and Experimental Therapeutics August 1, 1999, 290 (2) 847-853;
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