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Roles of PACAP and PHI as inhibitory neurotransmitters in the circular muscle of mouse antrum

  • Gastrointestinal Function
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Abstract

Mediators of neurogenic responses of the gastric antrum were studied in wild-type and pituitary adenylate cyclase-activating polypeptide (PACAP) -knockout (KO) mice. Electrical field stimulation (EFS) to the circular muscle strips of the wild-type mouse antrum induced a triphasic response; rapid transient relaxation and contraction, and sustained relaxation that was prolonged for an extended period after the end of EFS. The transient relaxation and contraction were completely inhibited by L-nitroarginine and atropine, respectively. The sustained relaxation was significantly inhibited by a PACAP receptor antagonist, PACAP6-38. The antral strips prepared from PACAP-KO mice unexpectedly exhibited a tri-phasic response. However, the sustained relaxation was decreased to about one-half of that observed in wild-type mice. PACAP6-38 inhibited EFS-induced sustained relaxation (33.5% of control) in PACAP-KO mice. Anti-peptide histidine isoleucine (PHI) serum partially (the 30% inhibition) or significantly (the 60% inhibition) inhibited the sustained relaxations in the wild-type and PACAP-KO mice, respectively. The immunoreactivities to the anti-PACAP and anti-PHI serums were found in myenteric ganglia of the mouse antrum. These results suggest that nitric oxide and acetylcholine mediate the transient relaxation and contraction, respectively, and that PACAP and PHI separately mediate the sustained relaxation in the antrum of the mouse stomach.

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Abbreviations

KO:

knockout

EFS:

Electrical field stimulation

PACAP:

Pituitary adenylate cyclase-activating polypeptide

NO:

Nitric oxide

VIP:

Vasoactive intestinal polypeptide

PHI:

Peptide histidine isoleucine

NANC:

Nonadrenergic, noncholinergic

FITC:

Fluorescein isothiocyanate

TTX:

Tetrodotoxin

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Acknowledgements

We thank Dr. G.S. Drummond (Wellspring Pharmaceutical Corporation, N.J., USA) for critical reading of this manuscript. This work was supported in part by Grants-in-Aid for Scientific Research (A), (B) and (C), and for Young Scientists (B) from Japan Society for the Promotion of Science, and through scholarships from Ono Pharmaceutical and ZERIA Pharmaceutical Co.

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Authors and Affiliations

  1. Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Science, Osaka Prefecture University, Sakai, Osaka, 599-8531, Japan

    Makiko Toyoshima, Tadayoshi Takeuchi, Hiroto Goto, Kazunori Mukai & Fumiaki Hata

  2. Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan

    Norihito Shintani, Hitoshi Hashimoto & Akemichi Baba

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  1. Makiko Toyoshima
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  2. Tadayoshi Takeuchi
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Correspondence to Tadayoshi Takeuchi.

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Toyoshima, M., Takeuchi, T., Goto, H. et al. Roles of PACAP and PHI as inhibitory neurotransmitters in the circular muscle of mouse antrum. Pflugers Arch - Eur J Physiol 451, 559–568 (2006). https://doi.org/10.1007/s00424-005-1491-6

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  • DOI: https://doi.org/10.1007/s00424-005-1491-6

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