Involvements of PHI-nitric oxide and PACAP-BK channel in the sustained relaxation of mouse gastric fundus.
The roles of nitric oxide (NO) and K(+) channels in sustained relaxation induced by electrical field stimulation (EFS) in the presence of atropine and guanethidine were studied in circular muscle strips of mouse gastric fundus. In the wild-type mouse, N(G)-nitro-l-arginine (l-nitroarginine), a nitric oxide synthase inhibitor, significantly inhibited the sustained relaxation in addition to the rapid relaxation. The sustained relaxation in pituitary adenylate cyclase-activating peptide (PACAP)-knockout mouse, which was smaller than that of the wild-type mouse, was also inhibited by l-nitroarginine. l-Nitroarginine inhibited the relaxation induced by the peptide histidine isoleucine (PHI), but not that induced by PACAP. S-Nitroso-N-acetyl-dl-penicillamine (SNAP), a NO donor, -induced relaxation was not affected by PACAP(6-38). EFS-induced sustained relaxation was inhibited by iberiotoxin, a big conductance calcium-activated K(+) (BK) channel inhibitor, but not by apamin, a small conductance calcium-activated K(+) (SK) channel inhibitor, and glibenclamide, an ATP-sensitive K(+) channel inhibitor. The relaxation that remained after the iberiotoxin-treatment was significantly inhibited by l-nitroarginine. Iberiotoxin inhibited PACAP-induced relaxation, while it had no effect on both PHI- and SNAP-induced relaxation. Immunoreactivities to anti-BK channel and anti-PHI antibodies were found in the circular muscle and the myenteric plexus layers, respectively. These results suggest interplay between PHI and NO in the sustained relaxation of the mouse gastric fundus, and that BK channels are involved in the PACAP-component of the sustained relaxation.
Hagi
Kiyomi
K
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531, Japan.
Azuma
Yasu-Taka
YT
Nakajima
Hidemitsu
H
Shintani
Norihito
N
Hashimoto
Hitoshi
H
Baba
Akemichi
A
Takeuchi
Tadayoshi
T
D000818:Animals; D004558:Electric Stimulation; D005748:Gastric Fundus / Q000502:physiology*; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D010451:Peptide PHI / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000502:physiology*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010451:Peptide PHI; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine