Pre- and post-junctional actions of prostaglandin I2, carbocyclic thromboxane A2 and leukotriene C4 in dog tracheal tissue

Abstract

Effects of carbocyclic thromboxane A2 (cTxA2), prostacyclin (PGI2) or leukotriene C4 (LTC4) on the membrane and contractile properties of the smooth muscle cells and on the excitatory neuro-effector transmission in the dog trachea were observed by means of the microelectrode, double sucrose gap and tension recording methods. cTxA2, PGI2 or LTC4 at a concentration of 10(-7)M had no effect on the membrane potential of smooth muscle cells of the dog trachea. At 10(-6)M, cTxA2 and LTC4 slightly depolarized, and PGI2 hyperpolarized the membrane. cTxA2 (greater than 2.7 X 10(-10)M) evoked a sustained contraction, while the amplitude of the twitch contractions evoked by field stimulation in the presence of indomethacin (10(-6)M) and propranolol (10(-6)M) was inhibited, dose-dependently. PGI2 (greater than or equal to 2.7 X 10(-7)M) reduced the muscle tone and the amplitude of twitch contractions evoked by field stimulations. cTxA2 or PGI2 (10(-10)-10(-7)M) reduced the amplitude of the excitatory junction potentials (e.j.ps) evoked by field stimulation with no change in the membrane potential, input membrane resistance or the sensitivity of the muscle cells to acetylcholine (ACh). LTC4 (1.6 X 10(-8)M) evoked a sustained contraction of the dog trachea; however, this agent did not affect either the amplitude of the twitch contractions or the e.j.ps evoked by field stimulation. The amplitude of the e.j.p. was dependent on the external concentration of Ca2+, and the inhibitory actions of cTxA2 on e.j.ps were partly overcome by increasing the concentrations of [Ca]o. When the amplitudes of e.j.ps were plotted against [Ca]o on a double log scale, the above relation yielded a straight line with a slope of 1.7 or 1.0, in the absence or presence of cTxA2, respectively. After treatment with Ca2+-free 2 mM EGTA-containing solution, cTxA2 or LTC4 did not evoke a contraction in the dog trachea, whereas ACh (10(-7)-10(-6)M) did. These results indicate that cTxA2 and PGI2 have dual actions on pre- and post-junctional membranes of the dog tracheal tissue, i.e. both agents inhibit the excitatory neuro-effector transmission in the dog trachea, presumably by inhibiting the release of ACh from the vagal nerve terminal. cTxA2 and LTC4 or PGI2 evoke contraction or relaxation of the muscle tissue, respectively, apparently through direct actions on the smooth muscle cells.