Adrenoreceptors and Ligand-Gated Ion Channels Overview

how many types of adrenoreceptors

Nine types including α and β subtypes.

β1 Receptors

• found in the heart

• increase heart rate and force of contraction

• gs coupled

β2 Receptors

• found in bonchial smooth muscle

• involved in bronchodilation and vasodilation

• gs coupled

pLGICs

• pentameric channels with five subunits in a ring

• second transmembrane domain from each subunit forms part of the channel lining

• 4 transmembrane domains

• large n terminal extracellular domain

Nicotinic Acetylcholine Receptors

• pGLIC

• cation channels permeable to Na+, K+, and Ca2+

• 16 different subunits

• 5 classes of subunit

pharmacological importance of nicotinic acetylcholine receptor

• blocking neuromuscular transmission

• used as relaxant in surgery

GABA-A Receptors

• pGLIC

• Chloride channels that hyperpolarize cells

physiological importance of GABA-A receptors

• main inhibitory neurotransmitter

• GABA-A are responsible for fast synaptic inhibition

• general anaesthetic

GABA-B vs GABA-A

• gpcr

• slower inhibition than GABA-A

ionotropic Glutamate Receptors families

NMDA, AMPA and kainate

NMDA Receptors are permeable to which ion

Highly permeable to calcium ions.

Structure of nAChRs

pentameric ligand gated ion channel with cys loop

structure of tyrosine kinase receptors

• single transmembrane domain

• present as dimers

• intracellular domain w tyrosine kinase domain

steps for tyrosine kinase receptor

• once agonist binds tyrosine kinase receptor dimerises

• tyrosine kinase domain becomes activaated

• phosphorylation of residues

• binds to intracellular adapter proteins and activates them

physiological importance of tyrosine kinase receptors

• regulation of growth and metabolism

• insulin receptor

• her2 receptor

what is function of her2 receptor

• regulation of epithelial cell division and differentiation

• used in breast cancer therapeutics

pharmacological importance of tyrosine kinase receptors

• synthetic insulin and insulin analogues

• target in therapeutics in cancer therapy (her2 receptor)

nuclear receptors function

• bind lipophilic agonists that pass through membrane

purpose of companion chaperone proteins

• bound to nuclear receptors

• helps them fold and remain stable

steps for binding to nuclear receptor

• once agonist is bound, chaperone protein disassociates

• receptor forms dimer that responds to specific sequences

• moves through nuclear pore

• influences transcription rate

  • transactivation or transrepression

structure of nuclear hormone receptor

• dna binding domain

• linked to ligand binding domain

  • by hinge region

physiological importance of nuclear receptors

• regulate basic functions

  • hormones - steroid sex hormones

examples of nuclear hormone receptors

• glucocorticoid

• mineralocorticoid

• thyroid hormone

main agonist to glucocorticoid receptors (nuclear hormone receptor)

cortisol

function and agonist of mineralocorticoid receptor

• regulate salt and water balance

• control bp

• aldosterone is main hormone

pharmacological importance of nuclear hormone receptors

steroid sex hormone receptors - target for drugs that modulate reproductive system eg oral contraceptive

glucocorticoid receptors - anti-inflammatory agents

mineralocorticoid receptors - target for cardiovascular conditions

thyroid hormone receptors - main treatment for hypothyroidism