Capsaicin can abolish spontaneous tone in guinea-pig trachealis

The properties of spontaneous tone in isolated preparations of guinea-pig tracheal smooth muscle were examined. Experiments with control preparations revealed that 5-15 min after stretching the muscle with 0.15 mN, the spontaneous tone assumed a plateau value from which it declined gradually during the following hour. During the plateau, the force amounted to approximately 35% and 1 h later to approximately 20% of a maximum KC1 contraction. The tone was independent of tetrodotoxin, atropine and propranolol. Indomethacin quickly and completely relaxed the tone in 15 of 21 preparations. However, four preparations retained some tone even after 1 h of treatment. Exposure to the C-fibre influencing drug capsaicin resulted in a dose-dependent, reversible suppression of spontaneous tone, normally preceded by a transient increase in force. No spontaneous tone at all remained after 1 h of 10 microM capsaicin. This effect was also found in preparations pretreated with tetrodotoxin, atropine and propranolol. Preparations, deprived of spontaneous tone by capsaicin-treatment, contracted distinctly when exposed to 10 microM arachidonic acid. This contraction was almost completely abolished by indomethacin, which indicates that the prostaglandin synthesis is functioning after capsaicin treatment and, thus, that inhibition of this synthesis is not responsible for the capsaicin effect. Exposure to phosphoramidon increased the spontaneous tone almost threefold. Addition of 3 nM neurokinin A in the permanent presence of capsaicin gave weaker contractions in preparations where prostaglandin synthesis had been abolished by indomethacin, as compared to contractions in preparations with intact prostaglandin synthesis. The data indicate that a continuous release of tachykinins from sensory C-fibres is essential for the generation of spontaneous tone and that a combination of tachykinins and prostaglandins determine the size of the tone in this preparation.