VIP antagonists enhance excitatory cholinergic neurotransmission in the human airway.
It has been reported that a low concentration of exogenously applied vasoactive intestinal peptide (VIP) suppresses the release of acetylcholine (ACh) from vagus nerve terminals in the ferret and feline trachea. There has been, however, no documentation of the prejunctional action of VIP in the human airway. We observed the effects of VIP and VIP antagonists on cholinergic excitatory neuro-effector transmission in the human bronchus to study the possible role of endogenous VIP on excitatory neurotransmission. In the human bronchus, VIP (10(-10) to 10(-7) M) showed no effect on either the contractions evoked by electrical field stimulation (EPS) or those evoked by ACh. To investigate the possible role of endogenous VIP on the human bronchus, we observed the effects of the VIP antagonists [4-Cl-D-Phe6,Leu17]-VIP and [Ac-Tyr1,D-Phe2]-GRF(1-29)-NH2 on excitatory neuro-effector transmission. Both VIP antagonists (10(-8) M) significantly enhances the contractions evoked by EFS without affecting the ACh sensitivity of smooth muscle cells. These results indicate that VIP antagonists have a prejunctional action that enhances excitatory neurotransmission. This study suggests that endogenous VIP may suppresses ACh release from the vagus nerve terminals in the human airway. It is also suggested that exogenously applied VIP may be inactivated by some mechanism in the human airway.
Aizawa
H
H
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Inoue
H
H
Shigyo
M
M
Takata
S
S
Koto
H
H
Matsumoto
K
K
Hara
N
N
D000109:Acetylcholine / Q000502:physiology*; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology*; D001980:Bronchi / Q000294:innervation*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D046508:Culture Techniques; D006801:Humans; D009130:Muscle, Smooth / Q000294:innervation*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*
D014660:Vasoactive Intestinal Peptide; D000109:Acetylcholine