Nonadrenergic, noncholinergic relaxation mediated by nitric oxide with concomitant change in Ca2+ level in rectal circular muscle of rats.
The mediators of nonadrenergic, noncholinergic (NANC) relaxation of the circular muscle of rat rectum were examined in vitro. In the circular muscle of rat rectum, NG-nitro-L-arginine (L-NOARG) at 10 microM did not affect electrical field stimulation-induced relaxation but at 100 microM it inhibited electrical field stimulation-induced relaxation by about 75% and 1-mM L-arginine reversed the inhibition. Exogenous nitric oxide (NO) (1-10 microM) concentration dependently relaxed the circular muscle. Electrical field stimulation increased the cyclic GMP content of the circular muscle to about twice its resting level. L-NOARG, even at 10 microM, completely inhibited the electrical field stimulation-induced elevation of cyclic GMP content. However, L-arginine at 1 mM did not reverse the inhibition in cyclic GMP content. Inhibitory junction potentials (i.j.ps) induced by electrical field stimulation in the circular muscle cells were not affected by L-NOARG, 100 microM. Apamin ( < or = microM) did not affect the electrical field stimulation-induced relaxation, but almost completely inhibited electrical field stimulation-induced i.j.ps. NO (0.3-10 microM) induced relaxation of the circular muscle with a concomitant decrease in intracellular Ca2+ level ([Ca2+]i). Abundant immunoreactivity of NO synthase was found in the circular muscle layer, in addition to myenteric and submucosal plexus. The results suggest that NO induces NANC relaxation with a concomitant change in [Ca2+]i in the circular muscle of rat rectum. However, the involvement of changes in cyclic GMP level and in membrane potentials in the mechanism was not shown in the present experimental conditions.
Department of Veterinary Pharmacology, College of Agriculture, Osaka Prefecture University, Sakai, Japan.
T
T
Takeuchi
S
S
Niioka
M
M
Kishi
T
T
Ishii
H
H
Nishio
F
F
Hata
T
T
Takewaki
K
K
Takatsuji
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004558:Electric Stimulation; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009197:Myenteric Plexus / Q000201:enzymology; D009479:Neuropeptides / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D026902:Potassium Channel Blockers; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D019335:Nitroarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; C047945:vasoactive intestinal peptide (10-28); D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D002118:Calcium