5. Receptor-Effector Coupling Mechanisms (2) Flashcards
What is type 2 receptor superfamily?
Indirect (g-protein mediated) linkage to ion channel or enzyme
What is an example of phospholipase-C beta?
Smooth muscle contraction
What is IP3?
A second messenger which causes release of pre-stored calcium from intracellular organelles into the cytoplasm
(the opposite of cyclic AMP)`
What does the elevated cytoplasmic calcium ion conc regulates?
Activity of contractile proteins in smooth cardiac muscle
Secretion from exocrine and endocrine glands
Release of neurotransmitters
Activity of many enzymes and ion channels
What is DAG?
A second messenger which activates a phosphorylating enzyme called Protein Kinase C
What are the processes regulated by phosphorylation of cellular proteins by PKC?
Contraction of smooth muscle Neurotransmitter Release of hormones from endocrine glands Receptor desensitization Ion transport across membranes Inflammation
What are examples of drugs targeting receptors coupled to Phospholipase C-beta by G-proteins?
Alpha1 adrenoreceptors (blood vessels) M3 muscarinic cholinoceptors (airway smooth muscle)
What are the agonists of alpha 1 adrenoceptors and examples?
Vasoconstrictors (noradrenaline/phenylephrine)
What are the antagonists of alpha 1 adrenoceptors?
Vasodilators
prazosin/doxazosin
What are the agonists of M3 muscarinic cholinoceptors?
Agonists are bronchoconstrictors (acetylcholine)
What are the antagonists of M3 muscarinic cholinoceptors?
Bronchodilators
ipratropium bromide, tiotropium
What is type 3 of receptor superfamilies?
Cell surface receptors that are enzymes (tyrosine kinase, guanylate cyclase)
What are examples of receptors of superfamily 3 that are linked to tyrosine kinase?
Insulin Receptor
Insulin- like growth factor receptor
Epidermal growth factor receptor
What are examples of receptors of superfamily 3 that are linked to guanylate cyclase?
Receptors for natruiretic peptides
Receptors for guanylin peptides
What is the structure of a receptor in superfamily 3?
Agonist binding site
N and C terminals connected by single transmembrane alpha helix
What is the significance of proteins changing shape during STM?
Shape change supports dimerization and coupling
What does MAPK?
Mitogen activated protein kinase
What are the characteristics of SH-2 domain-containing proteins?
Homologous to src oncogene product
SH-2 domain contains -100 amino acids
What are examples of SH-2 domain-containing proteins?
Glucose transporter proteins responsible for glucose uptake across the cell membrane
MAPK enzyme involved in cell proliferation, differentiation and survival pathways
Describe the JAK/STAT pathway
- Receptor does not prossess its own tyrosine kinase
- When agonist bind, receptor dimerizes and associates with cytosolic tyrosine kinase
- Jak phosphorylates the receptor dimer
- Phosphoylated receptor dimer is a binding site for transcription factor STAT
- STAT is phosphorylated, travels to nucleus and alters gene expression
Examples of drugs targeting tyrosine kinase linked receptor
Renal cancer drug (sunitinib)
Breast cancer drug (trastuzumab)
Look at slide 23
Proccesses
What is the action of natriuretic peptides?
Reducing the blood volume/pressure and returning to normal
Look at slide 25
And diferences
