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Tutorial 1 Receptors Cells must correctly interpret diverse external stimuli that regulate their behaviour. Precise control of physiological phenomena is achieved through a wide variety of receptor proteins located at the plasma membrane which bind and initiate the cellular response to these signals. These receptors can be classified into two main groups: (i) 7-transmembrane-spanning receptors. E.g. nucleotides, vasopressin. Heptahelical receptors (also called G-protein coupled receptors, GPCRs) form the largest family of cell-surface receptors known. Current estimates are that about 1% of the mammalian genome codes for these type of receptors and thousands of GPCRs are predicted to exist. A diverse array of external stimuli including neurotransmitters, hormones, lipids, odorants, taste ligands, nucleotides and calcium ions act through GPCRs giving rise to remarkably diverse physiological functions. They are characterised by a highly conserved structure comprising an extracellular N-terminus and an intracellular C-terminus separated by 7 helical transmembrane domains. Most function at the cell surface where they transduce extracellular signals into the cell by coupling to G-proteins (Guanine nucleotide-binding proteins – see tutorial 2). GPCRs can exist in either an active or inactive form. The inactive conformation is favoured in almost all cases and extracellular ligand binding causes a conformational changes in the GPCR. However, the nature of the physical changes in receptors that link agonist binding to downstream signalling events are not yet completely understood. Upon activation of GPCRs, they associate with distinct classes of heterotrimeric G-proteins (see Tutorial 2). Although there are a large number of G-protein subunits, most GPCRs can activate only a limited set of G-proteins. This is likely to have important consequences regarding control of the specificity of the signal. Recept