GPCR…
•C- and N-Teminus along with TM5/6 loop have higher degree of variability-
allow GPCRs to distinguish wide variety of ligands
GPCR…
• membrane bound
•Interact with G proteins through a ligand
• basic structure
• high degree of homology between TM regions therefore also called seven trans membrane (7TM) receptors
•Neurotransmitters
•Hormones
•Globular proteins for cell-to-cell communication
• Flow of information across plasma membrane
• Located mostly in the cell membrane
• Receive messages from chemical messengers coming from other
cells
• Transmit a message into the cell leading to a cellular effect
• Different receptors specific for different chemical messengers
• Each cell has a range of receptors in the cell membrane making it
responsive to different chemical messengers
•Chemicals released from nerve endings which
travel across a nerve synapse to bind with receptors on target cells,
such as muscle cells or another nerve
• short lived and
responsible for messages between individual cells
•Examples: •serotonin •histamine •dopamine
• complexity of molecules is no driving force for mediating GPCR function
•GPCR must obtain specific confirmation in order to propagate a signal
•Compounds that modulate PCR activity must be able to adopt the specific confirmation required by the binding side that they are targeting
•guanine nucleotide-binding proteins
• family of proteins that act as molecular switches inside cells
•transmit signals from a variety of stimuli from outside a cell to its interior
•activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine triphosphate
• belong to the larger
group of enzymes called GTPases.
•Membrane-bound proteins (3 broad families)
•Signal transduction
Basic structure:
•7 Transmembrane Domains (TMDs),
•3 intracellular loops (bind to G protein)
• 3 extracellular loops (bind to drug)
•N- and C-terminals
Family 2
•15 members
• Parathyroid hormone and glucagon receptors.
G-protein dependent…
• Machinery → Signal→ Carrier
(GPCR)- generates a signal, need a transmitter to send the signal
• Secondary messengers- molecules that transmit signals from GPCRs
to cellular machinery
• Two major types-
• cAMP system (cyclic adenosine monophosphate)
• Phosphatidylinositol system
phosphatidylinositol 4,5-bisphosphate →inositol-1,4,5-trisphosphate (IP3) and
diacylglycerol (DAG)
• norepinephrine play a role in memory attention stress reactions energy levels and the regulation of emotions
•Clonidine for attention deficit hyperactivity disorder anxiety disorders
•Dexmedetomidine is an anxiety reducing, sedative and pain medication
Neurotransmitters: Chemicals released from nerve endings which
travel across a nerve synapse to bind with receptors on target cells,
such as muscle cells or another nerve. Usually short lived and
responsible for messages between individual cells
Hormones: Chemicals released from cells or glands and which travel
some distance to bind with receptors on target cells throughout the
body