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Adrenergic Transmission Notes

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Adrenergic transmission
-released by post ganglionic sympathetic neurones which release noradrenaline from varicosities that make en passant synapses
-the target issue is inverated by multiple synaptic inputs from one fibre
-sympathetic innervations of sweat glands is an exception- as sympathetic neurons release ACH - act on muscarinic receptors
-Adrenal medulla: innervated by preganglionic sympathetic neurons, post synaptic target cells - chromaffin cells have nicotinic ACH receptors- release NA into the blood stream
-alpha receptors greater affinity to noradrenaline, B receptors have greater affinity for adrenaline Catecholamines: Noradrenaline, adrenaline, dopamine, isoprenaline Synthesis of noradrenaline/adrenalineL tyrosine, aromatic amino acid- actively taken up into adrenergic nerve varicosities by Na-dependent aromatic L-amino acid transporterTyrosine hydroxylase (cytoplasmic enzyme that is loosely attached to the endoplasmic reticulum) catalyses the conversion of tyrosine to Ldihydroxyphenylalanine (L-DOPA). The cofactors for this enzyme are Fe 2+ and tetrahydropteridine.The Km (affinity) is close to plasma concentration =

- The 1st hydroxylation step is the main control point for noradrenaline synthesis. Tyrosine hydroxylase inhibited by noradrenaline-end product of the biosynthetic pathway-Sympathetic nerve activity increases, synthesis increases-noradrenline competes for the biopterin binding site and reduces the tyrosine hydroxylase
-it is also inhibited by phosphorylation.
a-mehtyltryosine- competitive inhibitor of tyrosine hydroxylase, reduces the amount of NT-DOPA is converted into dopamine (neurotransmitter in the brain, gut and kidneys) by dopa decarboxylase o Carbidopa- peripheral inhibitor (doesn't cross blood brain barrier) used in parkinson's treatment to increase amount of L-Dopa Dopamine is then transported into synaptic vesicles by vesicular monoamine transporter--reserpine- binds to the amine binding site of the vesicular monoamine transporter and blocks the uptake of dopamine and depletes the store of noradrenaline- used as anti-hypertensive and acts in the periphery and brain- recovery requires new vesicles Dopamine B hydroxylase found in synaptic vesicles, converts dopamine into noradrenaline o Disulfiram-inhibits the enzyme so less noradrenaline synthesis/adrenaline synthesis

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