DUAL EFFECTS OF CATECHOLAMINES ON PRE‐ AND POST‐JUNCTIONAL MEMBRANES IN THE DOG TRACHEA

Abstract

Effects of noradrenaline or isoprenaline on the membrane and contractile properties of the smooth muscle cell, or on the excitatory neuro‐effector transmission in the dog trachea, in vitro, were observed by use of microelectrodes and double sucrose gap methods. Noradrenaline (<5 × 10−6 m) or isoprenaline (< 5 × 10−7 m) modified neither the membrane potential nor the membrane resistance. Increased concentrations of noradrenaline (> 5 × 10−5 m) depolarized and isoprenaline (> 5 × 10−7 m) hyperpolarized the membrane, and these actions were suppressed by phentolamine and propranolol respectively. Both catecholamines reduced the membrane resistance. Noradrenaline (5 × 10−6 m) or isoprenaline (5 × 10−7 m) reduced the resting tension, raised the mechanical threshold required to produce the contraction and suppressed the amplitude of phasic contractions evoked by electrical depolarization of the membrane. The action potential evoked by an outward current pulse in the presence of tetraethylammonium (TEA) was not affected by 5 × 10−6m isoprenaline, while the mechanical response was markedly suppressed. The excitatory junction potential (e.j.p.) evoked by electrical field stimulation was blocked by atropine. Noradrenaline (5 × 10−7 m) or isoprenaline (5 × 10−8 m) suppressed the amplitude of e.j.p. with no change in the membrane potential or input membrane resistance. Depression in the amplitude of e.j.ps produced by noradrenaline or isoprenaline reduced the amplitude of phasic contractions evoked by e.j.ps. These inhibitory actions of the catecholamines on mechanical responses and on e.j.ps were suppressed by pretreatment with propranolol (4 × 10−6 m). Dog tracheal smooth muscles are innervated by cholinergic excitatory and adrenergic inhibitory systems. Electrical field stimulation produced excitation of both cholinergic and adrenergic nerve fibres, and propranolol (4 × 10−6 m) enhanced the amplitude of e.j.p. generated by excitation of cholinergic nerves when repetitive stimulation (10 stimuli at 20 Hz) was used, but not the amplitude of the e.j.p. evoked by a single stimulus. 5‐Hydroxytryptamine (6 × 10−6 m) produced a tonic contracture of the dog trachea. After pretreatment with atropine (4 × 10−6 m), field stimulation (50 μs in duration and repetitive stimuli at 20 Hz) induced reversal of the contracture induced by 5‐hydroxytryptamine and this was abolished by propranolol (5 × 10−6 m). These results indicate that endogenous or exogenous catecholamines, in relatively low concentrations, predominantly activate β‐adrenoceptors in the pre‐ and post‐junctional membrane in the dog trachea, and induce muscle relaxation. 1982 British Pharmacological Society