Inhibitory actions of catecholamines on electrically induced contractions of the submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus

1 The submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus was used to study the actions of catecholamines on the twitch responses to electrical stimulation.

2 When the preparation was stimulated coaxially (0.1 Hz, 0.5 ms, supramaximal voltage), stable twitch-like contractions were obtained. These were abolished by tetrodotoxin (0.1 μM) and atropine (0.1 μM), potentiated by physostigmine (0.1 μM), and were mediated presumably by stimulation of intramural cholinergic nerves.

3 The twitch contractions of the muscularis mucosae were inhibited by catecholamines, in a concentration-dependent manner. The order of potency was isoprenaline > adrenaline > noradrenaline > dopamine.

4 The inhibitory actions of noradrenaline (1 μM) and adrenaline (1 μM) were partly reversed by phentolamine (1 μM) or by propranolol (1 μM), and completely abolished by both antagonists together. The inhibitory effect of dopamine (300 μM) was largely reversed by phentolamine (1 μM), but not by propranolol (1 μM), while the inhibitory action of isoprenaline was competitively antagonized only by propranolol (pA₂ of 7.6).

5 The contraction of the muscularis mucosae to exogenously applied acetylcholine (ACh, 20 nM) which was comparable in magnitude with that to electrical stimulation was also inhibited by isoprenaline (0.1 μM), adrenaline (1 μM) and noradrenaline (1 μM), but not by dopamine (300 μM). In the presence of propranolol (1 μM), noradrenaline, adrenaline and dopamine potentiated the ACh-induced contraction, while the effect of isoprenaline was mainly antagonized. The potentiating effects were antagonized by further treatment with phentolamine (1 μM).

6 Adrenaline, noradrenaline and dopamine but not isoprenaline, produced a weak contraction of the longitudinal muscularis mucosae in the presence of propranolol (3 μM). The contractile responses were completely inhibited by phentolamine (3 μM). Tone in the muscularis mucosae induced by carbachol (3 μM) in the presence of phentolamine (10 μM) was inhibited by catecholamines, in a concentration-dependent manner, an effect that was competitively antagonized by propranolol.

7 In the submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus there are three types of adrenoceptor, inhibitory prejunctional α-adrenoceptors, excitatory postjunctional α-adrenoceptors and inhibitory postjunctional β-adrenoceptors, and cholinergic neurotransmission is inhibited by catecholamines acting at both prejunctional α- and postjunctional β-adrenoceptors.