The role of nitric oxide in cholinergic neurotransmission in rat trachea.
1. We have investigated the role of nitric oxide (NO) in cholinergic contraction in rat trachea. 2. Methylene blue (10 nM to 30 microM) potentiated cholinergic contraction induced by electrical field stimulation (EFS) at 5 Hz in a concentration-dependent fashion. At a concentration of 30 microM, methylene blue decreased responses to log EFS frequency, producing 50% of maximum contraction from a control value of 0.74 +/- 0.09 Hz to 0.30 +/- 0.05 Hz without a significant effect on concentration-response curves to acetylcholine (ACh). 3. NG-monomethyl-L-arginine (L-NMMA; 100 microM) also potentiated cholinergic contraction induced by EFS at 5 Hz (131.5 +/- 4.6% of control) without having any effect against ACh (3 microM)-induced contractions. Likewise, L-NMMA (100 microM) significantly increased EFS (5 Hz)-evoked release of ACh from tracheal segments into the bath solution (51.4 +/- 4.0 pmol ml-1 in the presence of L-NMMA and 35.0 +/- 1.8 pmol ml-1 in the absence of L-NMMA, respectively). 4. Administration of NO (present in acidified solution of NaNO2) (1 nM to 10 microM) and sodium nitroprusside (100 nM to 10 microM) concentration-dependently reduced EFS (5 Hz)-induced cholinergic contractions without having a significant effect on ACh (3 microM)-induced contractions. These results were unaffected by prior exposure of the tissues to L-NMMA (100 microM). 5. Dibutyryl cyclic GMP (3 mM) also reduced cholinergic contractions induced by EFS at 5 Hz (70.1 +/- 3.6% of control) without any significant effect on ACh (3 microM)-induced contractions. 6. Pretreatment of tissues with capsaicin (30 microM) or a-chymotrypsin (1 u ml-') failed to inhibit methylene blue (30 microM)-induced potentiation of responses to EFS at 5 Hz.7. These results suggest that an endogenous NO-like factor may mediate prejunctional inhibition of cholinergic contraction through a cyclic GMP-dependent mechanism in rat trachea.
Sekizawa
K
K
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
Fukushima
T
T
Ikarashi
Y
Y
Maruyama
Y
Y
Sasaki
H
H
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D019323:omega-N-Methylarginine
D009479:Neuropeptides; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D003994:Bucladesine; D001120:Arginine; D000109:Acetylcholine; D008751:Methylene Blue