The Effects of Tetrodotoxin, Papaverine and Verapamil on the Increase in the Rate of Spontaneous Afferent Discharges Induced by Local Anesthetics from the Pulmonary Mechanoreceptors of the Bullfrog

Abstract

Procaine (1 × 10−5–1 × 10−4 M), dibucaine (1 × 10−5–1×10−4 M) and tetracaine (1 × 10−6–1 × 10−5 M) caused an increase followed by a decrease in the rate of spontaneous afferent (A) discharges (D) accompanied with a decrease in the flow rate of perfusion solution from the pulmonary vein in the isolated lung of the bullfrog, but these local anesthetics only decreased the rate of A.D. synchronized with lung inflation. The stimulatory effects of these drugs on the rate of spontaneous A.D. were studied. In the presence of TTX (1 × 10−7 M), the increase in the rate of spontaneous A.D. by local anesthetics was inhibited, but the decrease in the flow rate of perfusion solution by these drugs was not inhibited. Papaverine (1 × 10−5 M), which inhibited the decrease in the flow rate of perfusion solution by these local anesthetics, inhibited the increase in the rate of spontaneous A.D. by dibucaine, but not those by procaine and tetracaine. The inhibitory effects on the increase in the rate of spontaneous A.D. by these local anesthetics could be seen with verapamil in a concentration (1 × 10−4 M) which significantly inhibited the rate of spontaneous A.D., like TTX (1 × 10−7 M). Verapamil could not reverse the decrease in the flow rate of perfusion solution by these local anesthetics. From these results, the increase in the rate of spontaneous A.D. by procaine and tetracaine is due to not only the contractile effects of the drugs on the pulmonary vessel but also the direct stimulatory effects on the receptors which generate spontaneous A.D., and the increase in the rate of spontaneous A.D. by dibucaine may result from the contraction of the pulmonary vessel, and the stimulatory effect of dibucaine on the receptors would be weaker than that of procaine and tetracaine, since dibucaine could cause the increase in the rate of spontaneous A.D. only when dibucaine decreased the flow rate of perfusion solution.