18 - GPCRs in the CNS Flashcards
Sympathetic vs Parasympathetic response
SYMPATHETIC:
- wide pupils
- dry mouth
- deep breathing
- fast heartbeat
- high blood pressure
- emptying of energy reserves
PARASYMPATHETIC
- narrow pupils
- wet mouth
- shallow breathing
- slow heartbeat
- low blood pressure
- filling up of energy reserves
What are adrenal glands associated with?
The ADRENAL GLANDS are associated with the kidneys and produce hormones related to stress
What does the adrenal medulla do?
The ADRENAL MEDULLA secretes EPINEPHRINE (ADRENALINE) and NOREPINEPHRINE (NORADRENALINE)- CATECHOLAMINES
* They are secreted in response to stress-activated impulses from the nervous system
* They mediate various FIGHT-OR-FLIGHT RESPONSES
What do acetylcholine do to muscle?
Acetylcholine exerts down effect on muscle, so Ach responds to motor neurone stimulation to cause contraction of skeletal muscle
What does the sympathetic nervous system cause?
Sympathetic nervous stimulation causes secretion of Ach, preganglionic stimulation, which stimulates sympatheic nerves to release noradrenaline directly through synapses attached to many organs (postganglionic sympathetic stimulation)
Where is ACh secreted from?
Ach is secreted from nerve endings into the adrenal medulla, promoting the secretion of adrenaline and noradrenaline into the blood stream
What does long term stress result in?
Production of cortisol which is the principal glucocorticoid from the adrenal cotrex, and this is a response to hypothalamic stimulation of the anterior pituitary by CRH, causing secretion of ACTH into the blood interacting with receptors on the adrenal cortex causing elevation of intracellular cAMP increasing production of cortisol
GPCRs in the parasympathetic nervous system?
Preganglionic fibres (long) secrete Ach to stimulate nicotinic receptors on postganglionic receptors causing Ach actions of muscarininc receptors to stimulate rest and digest effects
GPCRs in the sympathetic nervous system
o Pre-ganglionic fibres (short) stimulate nicotinic receptors by Ach generating action potentials and post ganglionic fibres leading to the production of noradrenaline which acts of alpha- and beta-adrenergic receptors
o Beta receptors stimulate the heart and muscle and alpha shutting off non-essential supply
GPCRs in the CNS
- Ion channels- nicotinic receptors
- GPCR- muscarinic receptors, adrenergic receptors
Classification of cholinergic and adrenergic receptors
The adrenergic receptors (GPCRs) are divided into two major families, alpha and beta
o Beta class are Gs coupled receptors and they activate beta adrenergic receptors which there are three types beta1, 2 and 3
o Alpha receptors have more divisions, alpha 1 and alpha 2 which are subdivided further into ABC and ABD
What is the ligand gated ion channel receptor involved in?
LGIC Receptor-fast
o The nicotinic ACh receptor have two Ach binding sites which are very rapid allowing sodium entry into the neuronal cells to cause depolarisation
o And this is the nicotinic class
What is the G protein coupled receptor involved in?
G Protein-Coupled Receptor- Slower
o The muscarinic class
o Ach acts on the binding site between the transmembrane domains
How many isoforms of muscarinic types are there?
5 different isoforms
What types of nicotinic receptors are there?
There are neuronal and non-neuronal
GPCRs in the CNS
Noradrenaline and adrenaline lead to:
- Gq/11 –> alpha(1)-adrenergic [smooth muscle contraction (blood pressure rises), viscous saliva (dry mouth), goose flesh]
- Gi,0 –> alpha(2)-adrenergic [smooth muscle relaxation (blood pressure falls)]
- Gs –> beta-adrenergic [increased heart beat, glycogenolysis and lipolysis, relaxation of airway muscles, inhibition of peristalsis]
Beta-adrenoceptor activation by epinephrine
- Beta-adrenoceptors
- G-protein
- Enzyme- Adenylaye cyclase
- ATP -> cAMP
Beta-adrenoceptor activation by epinephrine in the heart
cAMP-> increases strength and rate of heartbeat (beta1)
Beta-adrenoceptor activation by epinephrine in the lungs
cAMP-> relaxes bronchial smooth muscle (beta2)
Pharmacology of beta-adrenoceptors
- agonists in the lung
- antagonists in the heart
Give an example of the pharmacology of beta-adrenoceptors as an agonist
Agonists in the lung: salbutamol (beta2 selective)
o Dilates bronchial smooth muscle
o Eases respiration
o Used in asthma
Give an example of the pharmacology of beta-adrenoceptors as an antagonist
- Antagonists in the heart: atenolol (beta1 selective)
o Competitive reversible antagonist
o Slows heart rate and reduces force of beat
o Used in cardiovascular disease, e.g, hypertension
Describe the mechanism of alpha1-adrenoceptor activation by epinephrine
- IP3 releases calcium from the sarcoplasmic reticulum
- DAG opens calcium channels to allow calcium entry
- Increase in intracellular free calcium
- Constraction of smooth muscle in walls of blood vessel -> constriction
Describe the pharmacology of alpha1-adrenoceptor
Prazosin- antagonist at alpha 1-adrenoceptor
* Prevents contraction of smooth muscle in blood vessel wall
* Blood vessel dilate
* Blood pressure falls
* Used in cardiovascular disease- e.g, hypertension
