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 pre parations revealed that 5-15 min after stretching the muscle with 0.15 mN, the spontaneous tone assumed a plateau value from which it declin ed gradually during the following hour. During the plateau, the force amounted to similar to 35% and 1 h later to similar to 20% of a maximu m KC1 contraction. The lone was independent of tetrodotoxin, atropine and propranolol. Indomethacin quickly and completely relaxed the tone in 15 of 21 preparations. However, four preparations retained some lon e even after 1 h of treatment. Exposure to the C-fibre influencing dru g capsaicin resulted in a dose-dependent, reversible suppression of sp ontaneous tone, normally preceded by a transient increase in force. No spontaneous tone at all remained after 1 h of 10 mu M capsaicin. This effect was also found in preparations pretreated with tetrodotoxin, a tropine and propranolol. Preparations, deprived of spontaneous tone by capsaicin-treatment, contracted distinctly when exposed to 10 mu M ar achidonic acid. This contraction was almost completely abolished by in domethacin, which indicates that the prostaglandin synthesis is functi oning after capsaicin treatment and, thus, that inhibition of this syn thesis is not responsible for the capsaicin effect. Exposure to phosph oramidon increased the spontaneous tone almost threefold. Addition of 3 nM neurokinin A in the permanent presence of capsaicin gave weaker c ontractions in preparations where prostaglandin synthesis had been abo lished by indomethacin, as compared to contractions in preparations wi th intact prostaglandin synthesis. The data indicate that a continuous release of tachykinins from sensory C-fibres is essential for the gen eration of spontaneous tone and that a combination of tachykinins and prostaglandins determine the size of the lone in this preparation.