Projects / Programmes
Pharmacology: experimental and molecular
January 1, 2004
- December 31, 2008
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| 1.09.00 |
Natural sciences and mathematics |
Pharmacy |
|
| Code |
Science |
Field |
| B740 |
Biomedical sciences |
Pharmacological sciences, pharmacognosy, pharmacy, toxicology |
NO, receptors, neurotransmitters, histamine, neurotrophic factors, cytokines, endothelins, signal molecules, ligands, antidepressants, central nervous system, isolated cells, isolated tissues, isolated organs, cell cultures, mechanisms of action, secretion, pharmacokinetics, ischemic preconditioning, electrostimulation,.
Researchers (31)
Organisations (1)
Abstract
Experimental pharmacology includes studies of effects of endogenous substances, drugs and other xenobiotics on organs and cells in physiological, pathological and changed conditions.
The research will continue the studies of the effects of endogenous substances (neurotrophic factors, transmitters and cytokines) and drugs on model systems: the whole animal, isolated organs and cells and on primary cell cultures in physiologic and changed conditions. Researches will be focused on the studies of not well understood mechanisms of actions of substances/drugs,cell signalling pathways and on pharmacological modulation of effects.
Endogenous transmitters act via receptors. We shall investigate interactions of histamine H1-receptor in blood vessels (on membranes of vascular smooth muscle and endothelium) with new specific agonists of H1-receptor (derivatives of histaprodifen) and mechanisms, involved in signal transduction through activation of histamine receptor on astrocytes. We also want to elucidate mechanisms involved in histamine release from mast cells induced by nerve growth factor (NGF) - the role of protein kinase and phospholipase C. Isolated stomach will be used in studies of histamine H2 antagonists and inverse agonists and the applicability of this model for studying secretory processes and drugs which influence them,will be established.
Using isolated trachea we shall try to elucidate mechanisms, involving histamine, which modulate its reactivity.
For functioning of cells, tissues and organs interactions between particular endogenous transmitters (neurotransmitters, neuromodulators, neurothrophic factors, cytokines) and also interactions of endogenous transmitters with active agents are important (e.g. psychotropic drugs with histamine).Therefore a part of the research will involve pharmacologic modulation of synthesis and secretion of NGF, brain-derived neurotrophic factor and other neurotrophins from neurones and non neurone-cells, an influence of histamine and interleukin 6 on the release of NGF, influence of histamine on the secretion of interleukin 6 and expression of interleukin receptors and part of the research the influence(s) of psychopharmaka, especially antidepressants on pharmacokinetics of histamine and its metabolite methylhistamine and also processes that are involved in this.
A part of the studies will be focused on drug action in changed conditions, since illness or chronic treatment with drugs can change target organs (such as remodelling of the heart muscle, a change in brain plasticity). In the study of brain plasticity, changes in the function of glial cells will be followed during development, after experimental brain injury (changed expression of receptors and molecules of extracellular matrix) and also whether the reaction to the influence of particular agents/transmitters (such as serotonin) in CNS is changed. In the models of injuries, induced by ischemia or with substances (for example with toxins), we study the protective action of drugs, such as calcium and endotheline antagonists, which act cardioprotectively. During the action of drugs and toxins and in changed conditions, the release of mediators is also changed and this influences the course of therapy. Therefore we shall measure the release of some mediators and markers that reflect the condition of heart and coronary vessels. The role of endothelium in the mechanism of drug action will be especially emphasized.
Experimental pharmacology includes also studying of unwanted effects of drugs, which arise either because of high doses or chronic exposure to therapeutic doses of drugs or to toxins from the environment. Therefore the group will continue to study the mechanism of cytotoxic effects of bee venom on endothelial cells.
We intend to use the following basic research methods: 1) for isolation of cells/intracellular units; 2) for cell culture preparation; 3) isolated organs with systems for measurement and analysing effects
Significance for science
The present program P3-067 joined all researches from the fields of pharmacology, who before year 2004 belong to two different research groups. The merge would result in better and faster development of scientific discipline and consequently better approach in development of drugs and biopharmaceuticals, new diagnostic devices and treatment approaches. Results of the research work performed between 2004 and 2008 elucidated the effects and mechanisms of action of endogenous and exogenous compounds (neurotransmitters like serotonin, immunomodulators e.g. histamine, cytokines; toxins (melittin and ethanol) in organisms in different physiological and pathological conditions. Some of the results pointed out the use of old drugs (new indications for already known and established medicines, which is also the world trend and goal) in clinical practice, other results will show new possibilities for future drug development. The most advantegous in this time period was also the cooperation of P3-067 program group members with other research groups that resulted in many excellent publications.
Significance for the country
This research program is of importance to broaden the knowledge, necessary for persistence and development of pharmacology. Development of pharmacology is crucial for parallel development of other disciplines in medicine, pharmacy, therapeutics and toxicology. Permanent development of pharmacology enables our equivalent participation and communication in the scientific and biomedical international community. For example – neurotrophic factors and their receptors are crucial drug targets in the therapeutics of neurodegenerative diseases, pain, and cancer. Researching this field will help our group to find more scientific contacts with foreign scientists and international research funding. Regardless, that we are doing mostly basic research, new contacts have been found with pharmaceutical industry and we already started developing new methods and techniques, which are basis for new drugs development and drug registration procedures. Results of the proposed research plan will widen the knowledge on drug action and to more rational drug use. Many of the results of the proposed research plan can lead to better pharmacotherapy or at least better knowledge and understanding of main and side effects of drugs, observed in clinical practice. When introducing new medicines to Slovenia, a good knowledge of pharmacology is crucial. The knowledge about basic mechanisms of drug action is helpful when introducing new drugs into pharmacotherapy. Some rare side effects can be more easily observed and reported. One of the national priorities is also to keep up and further develop research work at University level. Quality schools will enable good academic atmosphere, necessary for bringing up ambitious graduates, as well as educating future teachers of pharmacology and pharmacogenomics. The knowledge of pharmacology is essential for rational use of new, more and more expensive drugs in Slovenia and worldwide. Quality graduates with a broad knowledge of pharmacology are not needed just in biomedical sphere. They will find their place in pharmaceutical industry and in public administration dealing with complex procedures of drug registration and pharmacovigillance.
Most important scientific results
Final report,
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Most important socioeconomically and culturally relevant results
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