Pre- and post-junctional actions of procaterol, a beta 2-adrenoceptor stimulant, on dog tracheal tissue

Abstract

1. The effects of procaterol, a beta 2-adrenoceptor agonist, on excitatory neuro-effector transmission in the dog trachea were investigated and the findings were compared to those seen with isoprenaline, with microelectrode, double sucrose gap and tension recording methods. 2. Procaterol (10(-10)-10(-9) M) and isoprenaline (10(-9) M) had no effect on the resting membrane potential or on the input resistance of the smooth muscle cells of dog trachea. However with increased concentrations (greater than 10(-8) M), these agents hyperpolarized the membrane and decreased the input resistance of the membrane. 3. Procaterol (10(-10)-10(-7) M) and isoprenaline (10(-9)-10(-7) M) dose-dependently reduced the amplitude of the twitch contractions evoked by field stimulation in the combined presence of indomethacin (10(-5) M) and guanethidine (10(-6) M). In parallel with actions on twitch contractions, procaterol (10(-10)-10(-7) M) and isoprenaline (10(-9)-10(-7) M) reduced the amplitude of the excitatory junction potentials (e.j.ps), evoked by single pulse field stimulation in the dog trachea. 4. Procaterol (10(-8) M) had no effect on the post-junctional response of smooth muscle cells to exogenous acetylcholine (ACh) (10(-7)-10(-6) M). 5. Pretreatment with ICI-118551, a beta 2-adrenoceptor blocking agent, reduced the inhibitory action of procaterol on the amplitude of twitch contractions evoked by field stimulations in the dog trachea. 6. These results indicate that procaterol in low concentrations has a prejunctional action inhibiting the excitatory neuro-effector transmission in addition to a postsynaptic action, presumably by suppressing transmitter release from the vagus nerve terminals through beta 2-adrenoceptors in the dog tracheal tissue. The pre- and post-junctional actions of procaterol explain its potent bronchodilator effects in clinical use.