Modulation of cholinergic neurotransmission by the peptide VIP, VIP antiserum and VIP antagonists in dog and cat trachea.

Abstract

1. Comparative studies on the effects of vasoactive intestinal polypeptide (VIP), commercially available VIP antiserum or VIP antagonists [Ac-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP on excitatory neuroeffector transmission in the dog and cat trachea were performed with microelectrode, double sucrose-gap, and tension recording methods. 2. VIP (10(-11)-10(-9) M) had no effect on the resting membrane potential or on the input resistance of the smooth muscle cells of dog and cat trachea. However, with increased concentrations (greater than 10(-8) M) VIP hyperpolarized the membrane and decreased the input resistance of the membrane in both tissues. 3. VIP (10(-10)-10(-7) M) dose-dependently reduced the amplitude of the contractions evoked through the nervous structure excited by field stimulation in the combined presence of indomethacin (10(-5) M) and guanethidine (10(-6) M) in the dog, and in the presence of guanethidine (10(-6) M) in cat trachea. In parallel with actions on twitch contractions, VIP (10(-11)-10(-7) M) reduced the amplitude of the excitatory junction potentials (EJPs) evoked through the nervous structure excited by single pulse field stimulation in both tissues. 4. VIP (10(-9) M) had no effect on the post-junctional response of smooth muscle cells to exogenous acetylcholine (ACh) (10(-9)-10(-5) M). 5. During repetitive field stimulation at the stimulus frequency of 0.033-0.1 Hz, the amplitude of the EJPs was gradually reduced, and VIP (10(-9) M) enhanced this depression phenomenon in the dog and cat trachea. 6. EJPs also showed summation when repetitive field stimulation was applied at high frequency (20 Hz) in the dog trachea. The slope of the relationship between the relative amplitude of the EJP and number of stimuli at 20 Hz was 2.2 +/- 0.4 mV/stimulation (n = 4) in the dog trachea. However, in the cat trachea, summation of EJPs was not prominent, giving a mean slope of 0.6 +/- 0.2 mV/stimulation (n = 6) measured by the microelectrode method. VIP (10(-9) M) shifted downward the relationship between the relative amplitude of the EJP and the number of stimuli at 20 Hz in both tissues. 7. Overnight incubation with VIP antiserum (10(-6) g/ml) had little effect on the depression of the EJP in the dog and cat trachea, or the summation of the EJP observed in the dog trachea.(ABSTRACT TRUNCATED AT 400 WORDS)