Regional difference in the distribution of L-NAME-sensitive and -insensitive NANC relaxations in cat airway.
1. To investigate the distribution profile of functional inhibitory non-adrenergic non-cholinergic (i-NANC) nerves and the contribution of NO to the NANC relaxation in the cat, we studied the effects of N omega-nitro-L-arginine methyl ester (L-NAME) on NANC relaxation elicited by electrical field stimulation (EFS) in the trachea, bronchus and bronchiole. 2. EFS applied to the tracheal smooth muscle during contraction induced by 5-HT (10(-5) M) in the presence of atropine (10(-6) M) and guanethidine (10(-6) M) elicited a monophasic NANC relaxation. By contrast, NANC relaxation elicited in the peripheral airway was biphasic, comprising an initial fast followed by a second slow component and L-NAME (10(-5) M) selectively abolished the first component without affecting the second one. In the trachea, L-NAME (10(-5) M) completely suppressed the monophasic NANC relaxation when single or short repetitive stimuli (< 5) with 1 ms pulse duration were applied. However, at higher repetitive stimuli (> 10) with 1 or 4 ms pulse duration, suppression of NANC relaxation was incomplete. 3. In the small bronchi obtained from L-NAME-pretreated cats, EFS applied during contraction induced by 5-HT (10(-5) M) elicited only the slow component of NANC relaxation which is sensitive to tetrodotoxin. 4. In the peripheral airway, a newly synthesized VIP antagonist (10(-6) M) or alpha-chymotrypsin (1 U ml-1) considerably attenuated the amplitude of L-NAME-insensitive relaxation. 5. Single or repetitive EFS consistently evoked excitatory junction potentials (EJPs) in the central and peripheral airways. When tissues were exposed to atropine (10(-6) M) and guanethidine (10(-6) M), single or repetitive EFS did not alter the resting membrane potential. 6. These results indicate that at least two neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved in i-NANC neurotransmission and the distribution profile of the two components differs in the central and peripheral airway of the cat.
Takahashi
N
N
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tanaka
H
H
Abdullah
N
N
Jing
L
L
Inoue
R
R
Ito
Y
Y
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000502:physiology; D001980:Bronchi / Q000737:chemistry* / Q000166:cytology; D016084:Bronchoconstriction / Q000502:physiology*; D002415:Cats; D002918:Chymotrypsin / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology; D019331:NG-Nitroarginine Methyl Ester; D009433:Neural Inhibition / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D014132:Trachea / Q000737:chemistry* / Q000166:cytology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001120:Arginine; D002918:Chymotrypsin; D019331:NG-Nitroarginine Methyl Ester