Pre- and post-junctional effects of VIP-like peptides in guinea pig tracheal smooth muscle

To determine the role of VIP-like peptides on neurotransmission of vagus nerve, we evaluated the effects of helodermin, helospectin, and vasoactive intestinal peptide (VIP) on the contraction of guinea pig tracheal smooth muscle evoked by electrical field stimulation (EFS) or the exogenous application of actylcholine (ACh). Isometric tension of tracheal strips was measured in the presence of indomethacin (10(-6) M) and of guanethidine (10(-6) M). VIP (10(-9) M to 10(-7) M) significantly suppressed the contraction evoked by EFS. VIP, at concentrations of 10(-9) M and 10(-8) M, did not affect the ACh-evoked contraction, but a concentration of 10(-7) M suppressed ACh-evoked contraction. Helospectin and helodermin (10(-8) M and 10(-7) M) significantly suppressed the EFS-evoked contraction, but 10(-9) M showed no effect. Helospectin and helodermin had no effect on the ACh sensitivity of smooth muscle up to 10(-8) M, but a concentration of 10(-7) M suppressed the ACh-evoked contraction. These results indicate that helodermin, helospectin, and VIP exert both pre- and post-junctional inhibitory effects on the airway smooth muscle of guinea pigs. These peptides, thus, inhibited tracheal smooth muscle contraction prejunctionally at low concentrations, and acted postjunctionally at higher concentrations.