The effects of vasoactive intestinal polypeptide on cholinergic neurotransmission in an isolated innervated guinea pig tracheal preparation.

To explore the possibility that VIP modulates cholinergic neurotransmission in the airways, we studied the effects of exogenous VIP on contractile responses of an isolated innervated guinea pig tracheal preparation to vagal nerve stimulation (NS), electrical field stimulation (EFS) and exogenous acetylcholine (ACh). VIP (2.5 x 10(-8), 2.5 x 10(-7) M) caused concentration-dependent reductions in responses to NS and EFS. Low frequency stimulations (1 Hz) were significantly more inhibited than higher frequencies (5 and 20 Hz). VIP inhibited NS significantly more than EFS at 1 and 5 but not 20 Hz. In contrast, VIP (2.5 x 10(-7) M) did not significantly reduce responses to ACh (3 x 10(-7), 10(-6), and 3 x 10(-6) M). The neutral endopeptidase inhibitor phosphoramidon (5 x 10(-6) M) enhanced responses of NS to VIP but did not affect responses to NS in the absence of VIP. We conclude that in the isolated guinea pig tracheal preparation, VIP can modulate cholinergic neurotransmission by actions that are predominantly on post-ganglionic nerves but it has also a small additional effect on ganglionic transmission.