VIP antagonists enhance excitatory cholinergic neurotransmission in the human airway

Abstract

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.

Effect of vasoactive intestinal peptide (VIP)‐related peptides on cholinergic neurogenic and direct mucus secretion in ferret trachea in vitro

“…We have shown previously in ferret trachea in vitro that 2.5 Hz stimulation induces VIP release from cholinergic nerves, as evidenced by potentiation of [ 3 H]‐choline overflow by a VIP antibody or by α‐chymotrypsin, both of which interfere with the actions of VIP (Liu et al ., 1999). Similarly, in human airways in vitro , VIP receptor antagonists potentiate electrically‐induced contractions at 5 Hz (and also at higher frequencies) (Aizawa et al ., 1994). Thus, our own data and those of others indicate that VIP is released at comparatively low stimulation frequencies.…”

Neuroregulation by vasoactive intestinal peptide (VIP) of mucus secretion in ferret trachea: activation of BKCa channels and inhibition of neurotransmitter release

“…In the present study, a putative VIP 1 antagonist, [ D ‐p‐Cl‐Phe 6 ,Leu 17 ]‐VIP, did not alter the magnitude of cholinergic neural secretion nor did it diminish exogenous VIP‐induced mucus secretion. This antagonist has variable effects depending upon species and preparation ( Ellis & Farmer, 1989b ; Aizawa et al ., 1994 ; Shvilkin et al ., 1994 ), but is not suitable for investigating the role of endogenous VIP in neurogenic mucus secretion in ferret trachea.…”