Autonomic Pharmacology - Noradrenalin Synthesis, Release and Degradation Flashcards
Autonomic Nervous system organisation
The ANS is a part of the peripheral nervous system, conveying all output from the CNS to the rest of the body, except the motor innervation of skeletal muscle. Main 3 anatomical divisions: - Sympathetic - Parasympathetic - Enteric
What does the ANS regulate?
Smooth muscle tone, All exocrine secretion, Some endocrine secretions, Heart rate and force, Certain metabolic processes.
In the ANS how many neurones are between the CNS and the target organ?
2
What is the role of the sympathetic NS?
Fight and flight.
Causes: Iris dilation, increase salivation, decrease oral/nasal mucus, increase HR and force, dilate bronchial muscle in lungs, reduce GIT motility and increase sphincter tone.
What neurotransmitters are released the in pre and posts ganglion neurones in the parasympathetic NS?
Parasympathetic: Pre = ACh;
Post = ACh, NO
Synapse is midway/lower end between the spinal cord and the target organ.
What neurotransmitters are released the in pre and posts ganglion neurones in the sympathetic NS?
Sympathetic: Pre = ACh
Post = NAdh (Noradrenaline), ATP
Synapse is very close to the spinal cord.
In postganglionic sympathetic nerves what are the swellings seen in the terminal branches?
These swellings are where the neurotransmitters are stored.
Describe the synthesis of noradrenaline and adrenaline
Tyrosine (aa) -1- Dihydroxyphenylalanine (DOPA) -2-Dopamine -3- Noradrenaline -4- Adrenaline
Enzymes:
- Tyrosine hydroxylase
- DOPA decarboxylase
- Dopamine-B-hydroxylase
- Phenylehtanolamine N-methyl transferase
What is Tyrosine hydroxylase function in the synthesis of noradrenaline and adrenaline?
Converts tyrosine to dihydroxyphenylalanine (DOPA).
Rate-limiting step
Feedback inhibition by NAd
Inhibited by a-methyltryosine (it binds in the same site as the substrate, therefore blocking tyrosine).
What is DOPA decarboxylase function in the synthesis of noradrenaline and adrenaline?
Converts DOPA into dopamine.
Inhibited by carbidopa (inhibits DOPA in the periphery)
How does a-methyl tyrosine affect noradrenaline synthesis and what is it used to treat?
Inhibits tyrosine hydroxylase, that converts tyrosine into DOPA. It is used to treat Phaeochromocytoma (rare tumour of the adrenal gland tissue. Releases epinephrine and norepinephrine hormones that control HR).
How does Carbidopa affect noradrenaline synthesis and what is it used to treat?
Carbidopa is an inhibitor or DOPA-decarboxylase. It works in the periphery, not the CNS. It is used to treat Parkinson’s Disease (with L-DOPA). It decreases unwanted peripheral actions of administered L-DOPA.
How does Methyldopa affect noradrenaline synthesis and what is it used to treat?
Methyldopa is taken up by sympathetic neurones and is converted into a-methylnoradrenaline. It displaces the noradrenaline out of the vesicles and acts as a false transmitter. It is used to treat hypertension in pregnancy.
How is NAd and Ad stored in the adrenal glands?
NAd and Ad are not free in the cytoplasm, but are stored in subcellular membrane-limited particles (vesicles) known as chromaffin granules (300nm diameter).
What are the effects of reserpine drug on vesicular neurotransmitter stores?
Reserpine inhibits the vesicular amine transporter. Therefore stores of eg. catecholamine run down slowly as the amine leaks out. Stores fall to about 5% of the normal after 12 hours. Was used to treat hypertension.