Tribute to Alberto J. Kaumann

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 β₁- and β₂-AR using the subtype-selective antagonist. In addition, he showed that the dual coupling of β₂-AR to Gα_s- and Gα_i-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_s-proteins. His experiments with prostaglandin-E₁ 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.

Keywords: Cardiovascular adrenergic and serotonergic systems; cAMP; β-adrenoceptors.

Fig. 1

Top 15 contributors to Naunyn–Schmiedeberg’s Archives of Pharmacology. Red box marks position 6 for A. J. Kaumann. Adapted from Dats et al. (2023), with permission of the publisher

Fig. 2

Positive inotropic effect of serotonin in human left atrial preparations. Above: force of contraction (frequency of electrical stimulation 0.5 Hz) with increasing concentrations (in µM) of serotonin under control conditions (upper trace) and in the presence of the 5-HT receptor antagonist ICS 205–930 (tropisetron, 3 µM). Below: concentration–response curves for the above experiments (mean ± S.E.M, n = 6). From Sanders and Kaumann (1992) (with permission of the publisher)

Fig. 3

Action potentials (upper traces) and force of contraction (lower traces) of a kitten papillary muscle (stimulation frequency 0.2 Hz, 32.0–32.5 °C). A pre-drug control, B in the presence of sotalol (6 × 10⁻.⁴ M, 30 min). Please note the different time scales in (A) and (B). From Kaumann and Olson (1968) (with permission of the publisher)

Fig. 4

Left: PGE₁ effects on intact atria: chronotropic effects in spontaneously beating right atria (top) and inotropic effects (bottom). Data for PGE₁ in the presence of 100 nM propranolol are marked by an arrow. Right: Effects of (−)-isoprenaline (circles) and PGE₁ (triangles) in the absence (open symbols) or presence (closed symbols) of 100 nM propranolol on cAMP in membrane particles of atria from kittens. From Kaumann and Birnbaumer (1974) (with permission of the publisher)

Fig. 5

Schematic of two major contributions by Alberto Kaumann. The cardiac GPCR with the highest binding affinity for prostaglandin-E₁ (PGE₁), serotonin (5-HT), noradrenaline (NA), and adrenaline (Adr) are PGE₁-R, 5-HT₄-R, β₁-AR, and β₂-AR, respectively. All of them couple to Gα_s proteins, stimulate cAMP production, and increase spontaneous beating rate, but produce differential positive inotropic effects (PIE), suggesting compartmentation of cAMP production. Please note that activation of Gα_i by β₂-AR stimulation is restricted to mice overexpressing β₂-AR

Fig. 6

Alberto Kaumann in the Department of Pharmacology at the University of Murcia, Murcia, Spain (by courtesy of Dr. Alejandro Galindo-Tovar)