WEEK 1 Flashcards
What are the three main types of cell communication?
Autocrine, Paracrine and Endocrine signalling
What is autocrine signalling?
Secretory cell=target cell (intracrine=same but acts within same cell rather than binding to cell’s target sites)
What is paracrine signalling?
Secretory cell adjacent to target cell
What is endocrine signalling?
Substance secreted into general circulation and reaches target cell at a distance
What are the nicotinic effects of ACh?
muscle contraction, synaptic transmission (autonomic ganglia, parasympathetic postganglionic, CNS)
What are the receptors that cause nicotinic effects of ACh?
nAChRs (ion channels)
What are the muscarinic effects of ACh?
bradycardia, salivation, bronchospasm, mydriasis
What are the receptors that cause muscarinic effects of ACh?
M1-5 (GPCRs)
How do you measure ligand binding to a receptor?
Radioactive binding assay
Describe the process of radioactive binding assay
add radioactive ligand to sample containing receptor, wash, measure radioactivity
What is the equation for fraction of occupancy?
[Radioactive ligand]/[Receptor(total)]=[L]/[L]+Kd
What is the equilibrium dissociation constant (Kd) and what does it measure?
concentration of ligand where 50% of receptors are occupied by ligand=ligand affinity
What are the four main receptor types?
Ligand-gated ion channels (ionotropic)-eg. nAChRs
G-protein coupled receptors (metabotropic)-eg. mAChRs
Kinase-linked receptors-eg. cytosine receptors
Nuclear receptors-eg. oestrogen receptor
Process of GPCRs
Receptor in plasma membrane is bound by agonist, causes change in receptor conformation, activation, heterotrimeric G protein consistent of alpha, beta and gamma protein reassembles, active G protein receptors interact with G protein bound to plasma membrane by lipid anchors, G protein coupling, alpha, beta and gamma subunits dissociate causing nucleotide exchange-GDP moves off, GTP replaces it, activated G protein subunits regulate effector proteins, beta-gamma dimer formed which activates Ca2+ ion channels, GTP hydrolysis causes inactivation of Galpha protein
What effect does the Gs alpha subunit cause?
ATP-(adenylyl cyclase)->cAMP-(cAMP phosphodiesterase (PDE))->AMP
What effect does the Gq alpha subunit cause?
Gq->Phospholipase C->diacylglycerol-activates Protein Kinase C by binding of InsP3 to channels on ER surface, causing Ca2+ to move out and cause biological response
Describe the process of hormonal regulation of glycogen metabolism
Gs->AC->cAMP->Protein Kinase A
Protein Kinase A causes: Glycogen synthase phosphorylation (inactivation), Phosphorylase kinase phosphorylation (activation) which causes glycogen phosphorylase b to form glycogen phosphorylase a which causes glycogen hydrolysis in the liver
What is the role of Protein kinase?
Protein phosphorylation
What is the role of Protein phosphatase?
Protein dephosphorylation
TSH receptor signalling in the Thyroid with relation to the cAMP/PKA pathway
TSH binds to TSHR, causes Gs alpha subunit to activate adenylyl cyclase which forms cAMP from ATP, which activates Protein Kinase A (PKA), causing transcription of genes that form Tg-1, from which T3 and T4 are formed
What is an autonomous thyroid adenoma (ATA)?
benign tumour in the thyroid gland which causes hyperthyroidism-60% of cases due to activating TSHR mutation
What do homozygous muts suffer from and why?
Severe congenital hypothyroidism due to inactivating TSHR mutations
What do heterozygous muts suffer from and why?
Mild/compensated hypothyroidism due to inactivating TSHR mutations
What is the effect of positive feedback loops?
Stimulatory
What is the effect of negative feedback loops?
Inhibitory
What is a hormone?
A substance secreted directly into the blood by specialised cells which is present in minute concentrations and binds to specific receptors on target cells
What is homeostasis?
The maintenance of a constant internal environment
Describe the endocrine feedback loop
Stimulus activates Gland A which produces Hormone A, which activates Gland B/target tissue which activates Hormone B which causes action. Hormone B also causes inhibition of Gland A and Hormone A.
What are the two types of hormones?
Lipophilic (steroid hormones) and Water-soluble (peptide hormones)