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向阿尔贝托·J·考曼致敬。

Tribute to Alberto J. Kaumann.

作者信息

Christ Torsten, Ravens Ursula

机构信息

Institut für Experimentelle Pharmakologie und Toxikologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

Institut für Experimentelle Kardiovaskuläre Medizin, Universitätsklinikum Freiburg, Elsässerstrasse 4C, 79110, Freiburg, Germany.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct 18. doi: 10.1007/s00210-025-04708-5.

Abstract

This review summarises the major contributions of Alberto J. Kaumann who died in December 2024. The German-born pharmacologist devoted his scientific life to the cardiovascular adrenergic and serotinergic systems. He classified the subtypes of the cardiac β-adrenoceptors (β-AR) into β- and β-AR using the subtype-selective antagonist. In addition, he showed that the dual coupling of β-AR to Gα- and Gα-proteins plays a minor role in the healthy heart. He also found that the positive inotropic effect of serotonin (5-HT) was not mediated by release of noradrenaline, but due to activation of a specific 5-HT receptor coupled to Gα-proteins. His experiments with prostaglandin-E demonstrated an increase in cAMP and spontaneous beating frequency of the heart in the absence of a positive inotropic effect, suggesting a compartmentation of cAMP. This finding was later verified by experiments with subtype-selective phosphodiesterase inhibitors. Last not least, he explained the antiarrhythmic effect of sotalol by prolongation of the cardiac action potential duration, providing for the first time, what was years later to be defined as class III antiarrhythmic action. With Alberto Kaumann, we have lost a colleague and friend who had dedicated his life to science and music.

摘要

本综述总结了于2024年12月去世的阿尔贝托·J·考曼的主要贡献。这位出生于德国的药理学家将其科研生涯奉献给了心血管肾上腺素能和5-羟色胺能系统。他使用亚型选择性拮抗剂将心脏β肾上腺素能受体(β-AR)的亚型分为β₁-AR和β₂-AR。此外,他还表明β-AR与Gαs-和Gαi-蛋白的双重偶联在健康心脏中作用较小。他还发现,5-羟色胺(5-HT)的正性肌力作用不是由去甲肾上腺素释放介导的,而是由于与Gαq-蛋白偶联的特定5-HT受体的激活。他用前列腺素E进行的实验表明,在没有正性肌力作用的情况下,心脏中的环磷酸腺苷(cAMP)和自发搏动频率增加,提示cAMP存在分隔。这一发现后来通过亚型选择性磷酸二酯酶抑制剂的实验得到证实。最后同样重要的是,他通过延长心脏动作电位持续时间解释了索他洛尔的抗心律失常作用,首次提出了多年后被定义为III类抗心律失常作用的机制。随着阿尔贝托·考曼的离世,我们失去了一位将一生奉献给科学和音乐的同事与朋友。

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