Overview of Receptor Pharmacology

Abbreviations: A, adrenaline; NA, noradrenaline; DA dopamine; 5HT, serotonin, PLC, phospholipase C; IP3, inositoltrisphosphate; DAG, diacylglycerol; AC, adenylate cyclase; NI, not important; PKA, protein kinase A; COPD, chronic obstructive pulmonary disease; ACh, acetylcholine; MR, muscle relaxant Required information in bold. One agonist and antagonist per receptor is sufcient. Receptor family Adrenergic receptors Receptor subtype alpha 1 Physiological agonists NA > A Pharmacological agonists phenylephrine oxymetazoline Pharmacological antagonists prazosin Signalling mechanism Gq PLC IP3 + DAG Ca2+ Effect of agonist smooth muscle contraction, increased blood pressure decreased release of catecholamines from presynaptic neuron increased heart rate via PKAmediated increase in cardiac calcium channel activity Gs AC cAMP beta 2 A >> NA salbutamol terbutalin propranolol (non-selective) smooth muscle relaxation via phosphorylation of myosine increased lipolysis in adipose tissue, activation of brown adipose tissue used to treat asthma and COPD Note antagonists used as antihypertensives, agonists as decongestants presynaptic receptor, agonists used as antihypertensive agents agonists used to improve heart activity, antagonists to decrease its overactivation and as antihypertensives

alpha 2

A = NA

clonidine

NI

Gi AC cAMP

beta 1

A = NA

isoprenaline dobutamine

beta-blockers: propranolol (non-selective) atenolol (selective) pindolol (partial agonist)

beta 3

A > NA

NI

NI

possibly useful in the treatment of obesity

Information collated from http://www.iuphar-db.org/ Retrieved in March 2012.

Overview of Receptor Pharmacology

Receptor family Dopamine receptors Receptor subtype D1 Physiological agonists Pharmacological agonists NI Pharmacological antagonists NI Signalling mechanism Effect of agonist Note NI Gi AC cAMP

D2

DA

bromocriptine

antipsychotics: chlorpromazine haloperidol

inhibitory neurotransmission

agonists used to treat Parkinsons disease and excessive production of prolactin, antagonists are antipsychotics

D3 D4 Serotonin receptors 5HT1 5HT2 serotonin 5HT3

NI NI

NI NI

NI NI Gi AC cAMP

LSD

atypical antipsychotics: clozapine antiemetics: ondansetron

Gq PLC IP3 + DAG Ca2+ cation channel

stimulatory neurotransmission

receptor plays a role in hallucinations antagonists are used to combat vomiting during chemotherapy

NI

5HT4 Histamine receptors H1 histamine H2 NI anti-ulcer drugs: ranitidine NI antihistamines: loratadine

Gs AC cAMP Gq via beta-gamma subunits AC cAMP vasodilation, itching, bronchoconstricti on increased acid production in the stomach antagonists used to treat allergies

antagonists used to treat gastric hyperacidity and ulcers

Information collated from http://www.iuphar-db.org/ Retrieved in March 2012.

Overview of Receptor Pharmacology

Receptor family Cholinergic receptors Receptor subtype nicotinic (nAChR) Physiological agonists Pharmacological agonists nicotine succinylcholine decamethonium Pharmacological antagonists tubocurarine Signalling mechanism Effect of agonist Note cation channel membrane depolarisation excitatory transmission in autonomic ganglia and neuromuscular junction, antagonists used as nondepolarising MR, some agonists as depolarising MR mediates parasympathetic regulation of glandular secretion, ipratropium used in asthma, carbachol and pilocarpine to decrease intraocular pressure in glaucoma, pilocarpine also alleviates dry mouth mediates parasympathetic regulation of heart rate, atropine used to treat slow heart rate (bradycardia)

ACh M1 Gq PLC IP3 + DAG Ca2+ activation of glandular secretion

muscarine carbachol pilocarpine

atropine scopolamine hyoscyamine ipratropium Gi AC cAMP decreased heart rate via G-betagamma dimer mediated opening of K+ channels

M2

M3

Gq PLC IP3 + DAG Ca2+ Gi AC cAMP

M4

Information collated from http://www.iuphar-db.org/ Retrieved in March 2012.

Overview of Receptor Pharmacology

Receptor family Glutamatergic receptors Receptor subtype NMDA Physiological agonists Pharmacological agonists N-methyl-Daspartate Pharmacological antagonists ketamine phencyclidine Signalling mechanism cation channel (Na+ and Ca2+) Effect of agonist Note depolarisation, inux of calcium important in memory formation, excitotoxicity; antagonists cause dissociative hallucinations; only opens if glutamate is present AND membrane is depolarised

glutamate

AMPA kainate mGluR

AMPA kainic acid

cation channel cation channel G proteins

depolarisation depolarisation many roles in CNS; role in umami taste detection hyperpolarisation main inhibitory neurotransmitter

GABAergic receptors

GABAA

sedatives: benzodiazepines (BZD) barbiturates ethanol? GABA baclofen

picrotoxin umazenil (BZD antagonist)

chloride channel

GABAB

Gi AC cAMP

inhibitory transmission also via G-beta-gamma dimer mediated opening of K+ channels

Information collated from http://www.iuphar-db.org/ Retrieved in March 2012.

Overview of Receptor Pharmacology

Receptor family Voltage-gated sodium channels Receptor subtype NaV1.1 (neuronal bodies) NaV1.2 (fast, in axons) scorpion toxins aconitine tetrodotoxin local anaesthetics: lidocain cocaine tetrodotoxin Physiological agonists Pharmacological agonists Pharmacological antagonists Signalling mechanism Effect of agonist Note cation channel depolarisation

cation channel

depolarisation

depolarisati on

important in action potential propagation in nerve cells, specially axons

NaV1.4 (skeletal muscle) Voltage-gated calcium channels N-type or Q type (neuronal) L-type (long)

scorpion toxins

cation channel

depolarisation

NI

conotoxins

cation channel

depolarisation

important in synaptic exocytosis regulation responsible in part for in cardiac action potential, triggering Ca2+ release in skeletal muscle and contraction of vascular smooth muscles important for burst ring in neurons effects of opiates: analgesic, anti-anxiety, physical dependence

NI depolarisati on

nifedipine diltiazem verapamil

cation channel

depolarisation

T-type transient Opioid receptors mu delta kappa endorphins dynorphins enkephalins

NI

NI

cation channel

depolarisation

morphine

naloxone naltrexone

Gi AC cAMP plus other pathways

complex effects

Information collated from http://www.iuphar-db.org/ Retrieved in March 2012.