3 ECTS credits
75 h study time
Offer 1 with catalog number 4014841ENR for all students in the 1st semester at a (E) Master - advanced level.
This course comprises the following chapters:
These first two chapters deal with signaling molecules, basic approaches to study drug-receptor interactions and the structure and function of receptors. In the first chapter of this part signaling molecules (denoted as ‘chemical mediators’) are divided according to their mode of transmission (hormones, neurotransmitters) and according to their hydrophobicity (hydrophobic hormones which pass the cell membrane/ hydrophilic/large signaling molecules whose receptors are at the outside of the plasma membrane). The receptors for chemical mediators are divided in the ways they trigger the cell response (activation of G proteins, endogenous phosphorylation, opening of ion channels).
This chapter deals with ligand mediated ion channels. With two typical examples the action mechanism of these receptors is explained. It concerns nicotinic acetylcholine receptor that operate the opening of sodium channels involved in the contraction of skeletal muscles and the glutamate and GABA mediated ion channels that are involved in rapid signal transduction in neurons.
This chapter deals with G-protein coupled receptors. They represent a very large family of plasma membrane receptors that are involved in a very broad range of (patho)-physiological processes. It might therefore not surprise that about half of all the known commercial medicines exert their effects via these receptors. This chapter will explain the general mechanism of signal transduction of these receptors as well as their classification on basis of their structure/amino acid sequence. It also deals with widely used technical approaches to investigate the interaction between signaling molecules (and their synthetic analogues: agonists and antagonists) and their receptors.
The next category of receptors are the growth factor or tyrosin kinase receptors. The binding of their ligands i.e. growth factors activates their intrinsic property of endogenous phosphorylation. As their name indicates, the binding of these ligands are involved in the regulation of cell growth and division.
The last category of receptors are located intracellularly. They mainly recognize steroid hormones, which are apolar mediators that are able to cross the plasma membrane barrier.
These two chapters of the course deal with a more in-depth insight in the quantitative and molecular aspects of the ligand interaction with (mainly) G-protein coupled receptors. The following parts will be discussed:
Quantitative aspects and complexity of (radio) ligand binding. Herein we will discuss the interpretation of ‘heterogeneity’, meaning the existence of different receptor subtypes in the binding assay, ‘cooperativity’, receptor-G-protein coupling.
Subsequently typical functional experiments for GPCR and the corresponding quantitative aspects will be discussed (agonist concentration-effect curves …). Attention will also be paid to concepts such as partial and inverse agonists, intrinsic activity, amplification, spare receptors … This chapter will pay attention to the complex relation between ligand-receptor binding and the measured response such as the activation of G-proteins, formation of ‘second messengers’ and tissue effects (for instance contraction of a muscle). It will deal with the major models/theories that describe and/or explain this relation. They include (i) the linear model, (ii) the ‘non-linear model’ or ‘transducer’ model, (iii) the ‘one site two-state model’, (iv) the allosteric ternary complex model’.
This chapter describes by which mechanism synthetic antagonists can modulate and/or inhibit ligand mediated effects. It will deal with classical competitive antagonists, competitive ‘insurmountable’ antagonists, ‘allosteric modulators’, ‘allosteric antagonists’, ‘inverse agonists’ and functional antagonists. Subsequently the molecular mechanisms will be dealt that disrupt the agonist response. It concerns mechanisms of receptor phosphorylation, desensitization and internalization.
Originally it was thought that natural and synthetic agonists of a particular receptors induced the same cellular and biochemical responses. However, relatively recently it emerged that different ligand for one receptors can display selectivity to induce particular signal transduction pathways. In this chapter will be explained how this functional selectivity can be analyzed and whether certain ligand can be described as ‘biased ligands’.
In recent investigations it appeared that G-protein coupled receptor can occur as di- or oligomers. In this chapter will be discussed how this phenomenon can be demonstrated by recent molecular and biophysical techniques. It will also deal with the possible important consequences this can have for current molecular pharmacology.
All powerpoint slides of this cours are provided on the learning platform.
The general aim of the course is to provide the student insight in the domain of Molecular Pharmacology. The acquired knowledge during this course is useful in a research-oriented career. It provides the bio-engineers and biologists the basic knowledge to perform pre-clinical research and to function within multi-disciplinary teams in the pharmaceutical industry
Specific competencies:
Understand the meaning and content of pharmacological concepts.
Capable of handling in an independent and critical way of pharmacological knowledge
Use the acquired knowledge in the course to understand and critically read scientific publications in the domain of molecular pharmacology
During the lectures an active attitude is encouraged by which the theoretical knowledge can be applied in concrete examples
To be able to present orally in a short time period the essentials (aims, methods, results, discussion) of a scientific publication.
To have an opinion with relation to the discussion, interpretation and conclusions in a scientific publication
The final grade is composed based on the following categories:
Oral Exam determines 100% of the final mark.
Within the Oral Exam category, the following assignments need to be completed:
The oral exam of Molecular Pharmacology will consist of two parts:
Part 1: This part involves the discussion of a previously provided scientific article in the domain of the molecular pharmacology. The exam comprises a short (about 5 min) presentation by the student of this article which deals with the aim, methodology, results and conclusion(s). Subsequently the lecturer asks questions to assess the insight of the student in the related concepts. For this part about 1/2 hour is foreseen.
Part 2: A half hour before the oral exam the lecturer provides a general question related to the concepts presented during the lessons. The student discusses and answers this question and for this part about 1/2 hour is foreseen.
The exam is open book, so that the student is allowed to use all the information provided in the powerpoint slides of this course.
This offer is part of the following study plans:
Master of Biology: Molecular and Cellular Life sciences (only offered in Dutch)
Master of Biology: Education (only offered in Dutch)
Master of Biology: Molecular and Cellular Life sciences
Master of Teaching in Science and Technology: biologie (120 ECTS, Etterbeek) (only offered in Dutch)