Abstract
The positive chronotropic effect of (−)-isoprenaline in mouse atria was determined at 37 and at 26°C under control conditions and in the presence of the catechol-O-methyltransferase (COMT) inhibitor tropolone. Under control conditions, the atria were markedly more sensitive at the lower bath temperature (ED 50 37 °C/ED 50 26°C = 16.61). However, in the presence of tropolone, there was little difference in the sensitivity (ED 50 37°C/ED 50 26°C = 2.18). These data suggest that decreased activity of COMT at 26°C is a major factor in temperature-dependent supersensitivity. Support for this concept comes from studies with (−)-soterenol and (±)-nylidrin at 37°C and 26°C. Temperature-dependent supersensitivity was not observed with these agonists which are not substrates for COMT.
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