Summary
The effects of long-term incubation and of indomethacin on contractile responses to adrenaline and noradrenaline of the guinea-pig esophageal muscularis mucosae were studied in vitro.
In the presence of propranolol (3 μM), contractions of the isolated muscularis mucosae of the guinea-pig esophagus induced by adrenaline (10 μM) and noradrenaline (10 μM) gradually increased in magnitude with incubation time, and after 7.5 h reached a peak which was about 3 times the initial response. Contractions to adrenaline and noradrenaline observed at 2.5 h after the incubation was started were fully inhibited by phentolamine (3 μM) and prazosin (3 μM), and slightly by yohimbine (3 μM). These responses were also inhibited by polyphloretin phosphate (PPP, 30 μg/ml), indomethacin (1 μM) and aspirin (100 μM). The augmented contractions to adrenaline and noradrenaline observed at 7.5 h after the incubation was started were also inhibited by PPP, indomethacin and aspirin, while they were rather resistant to the blocking actions of phentolamine, prazosin and yohimbine.
The effect of matched concentrations of carbachol (0.1 μM), prostaglandin E2 (PGE2, 0.01 μM) and arachidonic acid (0.2 μM), which produced the same degree of contraction induced by catecholamines (10 μM), was gradually increased with incubation time. When the strip was treated with indomethacin (1 μM) throughout the experiment, contraction to arachidonic acid was abolished, that to carbachol was almost constant during long-term incubation but that to PGE2 was still increased after long-term incubation. Moreover, both concentration-response curves to carbachol and PGE2 examined at 7.5 h after the incubation was started were located to the left to those examined at 1.5 h after the incubation was started. In the presence of indomethacin (1 μM), the curve to PGE2, but not to carbachol, still shifted to the left after long-term incubation.
The present results demonstrated that the contractile responses of the guinea-pig esophageal muscularis mucosae were increased in magnitude depending on the incubation time. The mechanism of this augmentation may involve the development of atypical adrenoceptors, the stimulated arachidonic acid cascade and the increased responsiveness to PGs.
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Uchida, K., Kamikawa, Y. & Shimo, Y. Time-dependent augmentation of the contractile responses to adrenaline and noradrenaline of the guinea-pig esophageal muscularis mucosae in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 323, 114–120 (1983). https://doi.org/10.1007/BF00634258
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DOI: https://doi.org/10.1007/BF00634258