Catecholamines release mediators in the opossum oesophageal circular smooth muscle.

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Abstract
1. Effects of catecholamines applied exogenously to the circular smooth muscle layer of the body of the oesophagus of the opposum (Didelphis marsupialis) were studied, simultaneously measuring changes in the membrane potential, the membrane conductance and the contractility of the muscle, using the double sucrose-gap technique. 2. Superfusion of the smooth muscle with Krebs solution at 27.degree.C containing dopamine (10-6-10-4 M) dose-dependently caused a hyperpolarization of the smooth muscle cells and an increased membrane resistance followed after gradual repolarization by oscillations of the membrane potential, often accompanied by muscle action potentials. During the hyperpolarization, the tendency for the membrane potential to sag during prolonged application of hyperplorizing currents was reduced and the ''off'' depolarization following such currents was increased. This muscle did not develop active tension prior to treatment; it therefore did not relax during the hyperpolarizatons, but contracted following the depolarized phase of oscillations. 3. The non-adrenergic, non-cholinergic nerve-mediated inhibitory junction potential (i.j.p.) showed a small reduction in amplitude during superfusion with dopamine, explicable as a result of the drug-induced hyperpolarization. The ''off'' response following the i.j.p., decreased transiently when the membrane potential was hyperpolarized to its maximum value. Then it increased to values larger than control as the membrane repolarized. Vasoactive intestinal polypeptide (VIP, 10-6 M) produced a similar response but hyperpolarizations were smaller. 4. Of the tested catecholamines, isoprenaline, phenylephrine, butylated hydroxytoluene-920 (BHT-920) and clonidine were ineffective whereas the potency order for other catecholamines was dopamine > noradrenaline .gtoreq. adrenaline > DOPA. The catecholaMine-induced responses were not affected by .alpha.- or .beta.-adrenoreceptor antagonists given alone or in combination. Of the dopamine receptor antagonists tested domperidone was without effect, whereas haloperidol reduced and bulbocapnine blocked the response. The findings suggested that a receptor resembling DA1-type peripheral receptor mediated the effects of dopamine on opossum oesophagus. 5. The catecholamine-induced responses and those to VIP disappeared completely in Cl- free medium (Isethionate replacement). 6. Conditioning depolarization of the smooth muscle cells decreased but hyperpolarization increased the amplitude of the hyperpolarization (up to 20 mV). With larger hyperpolarizations the responses decreased and disappeared at around 50 mV hyperpolarization. 7. The catecholamine-induced responses were not affected by tetrodotoxin (TTX) but disappeared irreversibly after treatment with scorpion venom. At higher concentrations, scorpion venom produced electrophysiological effects like catecholamines. Lowering the Ca2+ concentration along with elevation of the Mg2+ concentration reduced both the i.j.p. and the response to dopamine to about the same extent. 8. It is concluded that the catecholamines in this preparation induce a release of mediator, which is VIP like, from nerve varicosities without evoking action of potentials.