Davy M, Grandcourt O, Midol-Monnet M, Cohen Y
Laboratoire de Pharmacologie, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
Cell Mol Life Sci. 1997 Mar;53(3):263-6. doi: 10.1007/pl00000601.
The positive chronotropic effect of a high concentration of 5-hydroxytryptamine (5-HT) in rat isolated atria results mainly from a tyramine-like mechanism and is linked to an increase in cAMP production by an indirect stimulation of beta-adrenoceptors. Using this preparation, we have compared the action of tyramine and 5-HT. The tyramine (0.15 microM)-induced increase in atrial rate was suppressed by atenolol (a beta 1-blocking drug) and by nadolol (a beta 1 beta 2-blocker), while the positive chronotropic effect of 5-HT was reduced by atenolol and suppressed by nadolol. The 5-HT-induced elevation in cAMP was unchanged in the presence of atenolol and abolished by nadolol. The involvement of beta 2-adrenoceptors in the effects of 5-HT could result from competition between 5-HT and noradrenaline at the beta 1-adrenoceptors that results in a fixation of noradrenaline on beta 2-adrenoceptors.
高浓度5-羟色胺(5-HT)对大鼠离体心房的正性变时作用主要源于一种类似酪胺的机制,并且通过间接刺激β-肾上腺素能受体与环磷酸腺苷(cAMP)生成增加有关。利用该制剂,我们比较了酪胺和5-HT的作用。阿替洛尔(一种β1受体阻断药)和纳多洛尔(一种β1β2受体阻断剂)可抑制酪胺(0.15微摩尔)诱导的心房率增加,而阿替洛尔可降低5-HT的正性变时作用,纳多洛尔则可抑制该作用。在阿替洛尔存在的情况下,5-HT诱导的cAMP升高未发生变化,而纳多洛尔可使其消除。5-HT作用中β2肾上腺素能受体的参与可能是由于5-HT与去甲肾上腺素在β1肾上腺素能受体处竞争,导致去甲肾上腺素固定于β2肾上腺素能受体。