Winners of the Nicolaus Copernicus Polish-German Research Award

Prof. Malinowska and Prof. Schlicker are specialists in pharmacology and physiology. Their major research interests include cannabinoid receptors and their action. Their joint research efforts are focused on molecular, biological and pharmacological description of cannabinoid receptors, in particular the neurochemical and molecular basis for cannabinoidal effect on brain. These studies are of considerable importance for explaining disorders of the nervous system.

Their cooperation dates back to 1991 when Prof. Malinowska served her post-doctoral internship (as a holder of scholarship awarded by the Alexander von Humboldt Foundation) at the University of Bonn. Over time, the projects initiated by them involved more and more of young researchers from both Poland and Germany. Together they published over 30 articles in the leading professional journals.

The winners of the 1^st edition of the COPERNICUS Award are also interested in the  physiology and pharmacology of the circulatory system. The major common areas of research of Prof. Barbara Malinowska and Prof. Eberhard Schlicker is to determine the functions of atypical ß-adrenergic and cannabinoid receptor in the regulation of the circulatory system. Prof. Schlicker conducts also research into the functions of cannabinoids in the central nervous system. In her research related to cannabinoid receptors, Prof. Malinowska works also closely with Prof. Manfred Göthert, Director of the Institute of Pharmacology and Toxicology at the University of Bonn (where Prof. Schlicker is based) and President of the Federation of European Pharmacological Societies (EPHAR).

Cannabinoids are chemical substance which originally were considered to be derivable from plants only and associated with Indian hemp. It was – among other things – marijuana produced from Indian hemp that helped accumulate knowledge on the mechanism of cannabinoid action (they affect so-called cannabinoid receptors which are located e.g. in the central nervous system, in the regions responsible for memory, sleep-wake patterns, emotions and body posture). Over time, human beings and animals (e.g. rats) were also found to have endogenous cannabinoids with anandamide as their main and best known representative. The interest in cannabinoids present in human beings and animals increased significantly over the recent years as it was shown that the plasma concentration of anandamide ? a potent agent reducing blood pressure which is released from blood platelets and macrophages ? rapidly increases in some pathological conditions, such as septic or haemorrhagic shock, myocardial infarction and cirrhosis. The studies completed under the supervision of Prof. Malinowska in cooperation with the Institute in Bonn showed at least five different sites which could potentially be affected by synthetic or endogenous cannabinoids on the circulatory system. It was also demonstrated that while septic shock causes the weakening of pre-synaptic functions of cannabinoid receptors located at the endings of sympathetic fibres which innervate the resistance blood vessels in rats.

As a result of their experiments and studies, the awarded scientists intend to explain the new mechanisms involved in regulating the circulatory system. Currently, they have concentrated their main efforts on the assessment of cannabinoidal impact on the contraction of human isolated pulmonary artery and functions of cannabinoid receptors (located at the endings of sympathetic fibres which innervated blood vessels and the heart) in pathological conditions ? including haemorrhagic and cardiogenic shock. Aside from the contribution of these studies to the general knowledge, they can also be of practical significance as indicated by the above-mentioned involvement of endogenous cannabinoids in the pathology of septic shock. Additionally, they can also enable demonstrating the undesirable effects of the drugs which are already on the market, e.g. drugs used in the treatment of obesity, nicotine and alcohol addictions.

Equally important is the second area of research related to atypical ß-adrenergic receptors. As soon as 1996 Prof. Malinowska and Prof. Schlicker showed that the cardiac contraction frequency in rats is stimulated to a great extent and on a long-term basis by the so-called ß-adrenergic receptors. In the same year, based on the studies of Prof. Alberto J. Kaumann of the Cambridge University, it was shown that the same mechanism applies to the stimulation of human heart. Over time, a range of different research groups showed that atypical ß-adrenergic receptors are stimulated or inhibited by blockers of ß-adrenergic receptors, such as Pindolol, Bucindolol, Alprenolol or Carvedilol.

A Polish-German team supervised by Prof. Malinowska in the Institute of Experimental Physiology at the Medical University of Białystok and Prof. Eberhard Schlicker in the Institute of Pharmacology and Toxicology at the University of Bonn is thus far the only group in the world which is researching the functions of atypical cardiac ß-adrenergic receptors in vivo, i.e. within the entire body of rats. The researchers are also interested in the effects of receptor-stimulants on the function of blood vessels, both isolated (e.g. human pulmonary arteries) and in vivo, comparing at the same time their impact on the heart and blood vessel parameters.

Further research projects are aimed at finding new potent agents stimulating or inhibiting the action of these receptors. They are supported by an additional group under the supervision of Prof. Katarzyna Kieć-Kononowicz of the Department of Technology and Biotechnology of Medicinal Agents at the Collegium Medicum of the Jagiellonian University in Cracow. The group is synthesizing compounds whose affinity to ß-adrenergic receptors is then investigated in the Institute of Pharmacology and Toxicology at the University of Bonn, while functional studies on animals are being carried out in Białystok.