Endocrinology 2 - Receptors and Second Messengers Cellular Communication - No cell exists in isolation (surrounded by a membrane, permeable to everything important) - Signals are sent between cells and the environment and processed - Signals are generally transmitted through the environment in the form of soluble molecules o Must be able to detect the molecule in the right concentration - These molecules are detected, and a response is produced - The biggest barrier is the cell membrane o The membrane is impermeable to big soluble molecules o Also, if it's charged - Some molecules are transported across the membrane and produce a signal o Only detected inside the cell e.g. steroid cells - Others are detected outside and a signal is transmitted - This is the role of the receptors - Ligand comes from the Latin word for 'binding' o A molecule that binds to a receptor (could be the signal molecules) - The ligand of the insulin receptor is insulin - Some receptors have one ligand whilst others can have many o Antihistamines (stop histamines binding and stop allergic reactions) o Some receptors have no ligands (or may not have been discovered) - One receptor can produce different responses based on the ligand - Receptors are generally transmembrane proteins o They have binding sites/grooves which accept the ligand - The extracellular region is where the ligand binds - The intracellular region interacts with the effectors - Thousands of receptors exist in humans o E.g. G-protein receptors - Detect an array of signals such as; o Light, smell, taste, hormones, neurotransmitters, sugars, fats, drugs Definitions Intracellular mediators - proteins that transmit signals from the receptor to the effector Effector enzymes - bring about change in the cell resulting in the (and affected by) production of second messengers Second Messengers - alter metabolism or affect effector enzymes Target Proteins - alter gene expression and cell behaviour Not every signalling pathway will contain all of these components
Receptor signalling cascades - Can detect a single molecule of ligand e.g. a photon Not particularly powerful signal o as its one receptor activated by a single photon of light - Then transduce this signal across a membrane - Rapidly amplify this signal - Activate a cascade of proteins that bring about appropriate cell behaviours Pathway for light - Protein called rhodopsin sits on the cell membrane o Is part of the GPCR family - Rhodopsin doesn't bind to a ligand; it has a ligand already stuck inside it o Chromophore called retinal - Photon hits the retinal and causes a cistransomaforalisation (bent to straight) - This changes the shape of the receptor and then changes it shape inside the membrane - Opening up a binding pocket - Binds to a G-protein (cytoplasmic mediator) - Acts as a molecular switch o Exchanges GDP for GTP - Activates another protein - cyclic GMR phosphodiesterase o Which breaks down phosphodiester bonds o Cyclic GMP becomes just linear GMP - 1 photon activates 5fifi G-protein molecules -