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Molecular Pharmacology

Class at Faculty of Science |
MC250P43

Syllabus

Lectures

The historical development of understanding of hormonal receptors (since Paul Ehrlich and John Newport Langley)

Discovery of adenylylcyclase and cAMP (Earl Sutherland) = the key stone of molecular endocrinology and pharmacology

Membrane receptors ? classification; ligand, agonist, antagonist, partial agonist, inverse agonist

Radioisotopes in medicine and biology, liquid scintillation, beta and gama counting, Bq, Ci, radioligand, specific radioactivity, chemical stability of the radioligand, radiochemical stability

Ligand binding studies of membrane receptors, specific radioligands, saturation binding isotherm, Scatchard plot, calculation of Bmax and Kd values, allosteric and co-operative models of receptor-ligand interactions, Hill coefficient; criteria of Pedro Cuatrecassas for identification of receptor with the specific radioligand binding site

Why there are so many receptors for the single hormone or neurotransmitter? Heterogeneity of G protein coupled receptors (GPCR), splicing variants of 7TM receptors

Trimeric GTP binding regulatory proteins (G-proteins), discovery of trimeric G proteins (Martin Rodbell and Alfred G. Gilman)

Classification of the five main families of trimeric G proteins

Phosphoplipases C, phospholipases A2, phosphodiesterases and secondary messengers

Desensitisation of hormone response, internalisation, recycling and down-regulation of GPCR; internalisation and down-regulation of trimeric G proteins, cross-talk phenomena, membrane domains (Neubig, R. R. (1994) Membrane organisation in G-protein mechanism. FASEB J. 8, 939-946), feed-back regulations, multiple signalling cascades initiated by the same hormone or neutrotransmitter.

Sodium plus potassium activated, magnesium dependent adenosine triphosphatase (Na,K-ATPase), sodium pump, [3H]ouabain as specific marker of plasma membranes

Subcellular fractionation by differential and density-gradient centrifugation; isolation of plasma membranes and other subcellular particles; plasma membrane markers and enzyme activities.

Annotation

Lecture presents information about basics of molecular pharmacology, area of basic research dealing with characterisation of hormonal receptors and their signalling cascades with the help of biochemical, pharmacological and cell physiology approaches. Main discoveries in this field will be analysed in more details from historical perspective.

Lectures - in Czech -