MODULATION OF NEURAL BRONCHOCONSTRICTOR RESPONSES IN THE GUINEA-PIG RESPIRATORY-TRACT BY VASOACTIVE-INTESTINAL-PEPTIDE

Vasoactive intestinal peptide (VIP) is localised to cholinergic nerves in airways. We have investigated the effects of VIP on both cholinergic and non-adrenergic, non-cholinergic (NANC) neuronal bronchoconstrictor responses to electrical field stimulation (EFS) in guinea pig airways and on cholinergic neurotransmission following sensory nerve depletion. VIP significantly attenuated the cholinergic bronchoconstrictor responses to EFS in trachea (EC50 values in upper and lower trachea of 3.7 +/- 0.2 x 10(-9)M and 8.6 +/- 0.3 x 10(-9)M, respectively) and bronchi (31.2 +/- 1.6% inhibition in main and 15.1 +/- 3.3% in hilar bronchi at 10(-7)M VIP) and the NANC bronchoconstrictor responses to EFS in bronchi (with maximum inhibitions of 93.1 +/- 1.8% at 3 x 10(-8)M VIP in main and 40.2 +/- 5.3% at 10(-8)M in hilar bronchi). VIP at 10(-7)M, but not at 10(-10)M, significantly attenuated the contractile responses to exogenously applied ACh in trachea (EC50 values of 4.9 +/- 0.2 x 10(-6)M in the absence and 8.4 +/- 0.4 x 10(-5)M in the presence of VIP 10(-7)M VIP) to SP in main bronchi (EC50 values of 5.7 +/- 0.2 x 10(-8)M in the absence vs. 7.3 +/- 0.3 x 10(-7)M in the presence of 10(-7)M VIP). Since the inhibition of these neural responses is greater than the inhibition of the equivalent responses elicited by the exogenous transmitters, this indicates that VIP may modulate release of acetylcholine from cholinergic nerves and of neuropeptides from sensory nerves, in addition to a post-junctional functional antagonist action.