Autonomics Flashcards
Autonomic nervous system function
Regulate functions not under voluntary control: respiration, circulation, thermogenesis, heat dissipation, GI function
Efferent nerves
Both sympathetic and parasympathetic have two neurons: pre- and post-ganglionic neurons, interacting at autonomic ganglion
Structures not innervated by parasympathetics
Peripheral blood vessels, adrenal medulla, skin
Pharmacologic targets at cholinergic junction
Uptake- Hemicholinium Storage- Vesamicol Release- Botulinum toxin Termination- AChE inhibitors Receptors- agonists, antagonists
Neurotransmitter of pre-synaptic neuron
Acetylcholine for both sympathetic and parasympathetic
Neurotransmitters for post-synaptic neurons
Parasympathetic- ACh
Sympathetic- ACh, norepinephrine, dopamine
Production of acetylcholine
Choline uptake by Na+/choline cotransporter, choline and acetyl coenzyme A catalyzed to ACh by choline acetyltransferase, ACh transported into granules for storage
Release of acetylcholine
Action potential triggers fusion of membranes, release ACh into synpatic cleft, ACh binds and activates presynaptic or postsynaptic nicotinic or muscarinic receptors, ACh is broken down by ACh esterases in synaptic cleft
Muscarinic acetylcholine receptors
G-protein coupled receptors
Nicotinic acetylcholine receptors
Ligand-gated ion channels
Pharmacologic targets at adrenergic junction
Synthesis- Metyrosine Storage- Reserpine Release- Bretylium, guanethidine Reuptake- Cocaine, TCA, Ang II Receptors- agonists, antagonists
Reserpine
Used clinically to treat hypertension in third world countries
Enzymes that degrade catecholamines
COMT- present in kidney, liver, GI tract, other organs
MAO- present in neural tissue
Sympathomimetics
Tyramine, amphetamines, ephedrine, are poor agonists of adrenergic receptors
Norepinephrine reuptake
Taken up by NET, transported into vesicles by VMAT, displaces NE which is transported to cleft by NET
Production of norepinephrine
Tyrosine uptake by Na+/tyrosine cotransporter, tyrosine hydroxylase converts tyrosine into DOPA, DOPA converted to dopamine by dopamine decarboxylase, DA transported to granules and converted to NE by DA-beta-hydroxylase
Release of NE
Action potential triggers membrane fusion, release of NE into synaptic cleft, NE binds and activates presynaptic or postsynaptic adrenergic, serotonin, or dopamine receptors, reuptake of NE by presynaptic transporters
M2 cholinoceptor
Found in the heart, results in Gi activation (decreases cAMP)
M3 cholinoceptor
Found in exocrine glands, vessels, iris circular muscle, results in Gq activation (IP3, DAG)
Nn cholinoceptor
Located in autonomic ganglia, adrenal medulla, result in opening of Na, K channels, depolarization
Nm cholinoceptor
Found in skeletal muscles, open Na, K channels, depolarization
Alpha1 adrenoceptor
Located in smooth muscles, iris radial muscle, result in Gq activation (IP3, DAG)
Alpha2 adrenoceptor
Located in presynaptic, smooth muscle, causes Gi activation (decreases cAMP)
Beta1 adrenoceptor
Found in heart, juxtaglomerular apparatus of renal tubule, activates Gs (increases cAMP)
Beta2 adrenoceptor
Found in smooth muscles, heart, activates Gs (increases cAMP)
Heteroreceptors
Receptors that respond to substances released from adjacent neurons or cells, opposite to autoreceptors
Adrenergic presynaptic alpha2 receptors
Autoreceptor that negatively regulates the release of NE when NE levels get too high, inhibits inward calcium current that causes vesicular fusion and transmitter release
Phenoxybenzamine (POB)
Adrenal gland produces NE and Epi, POB indicated for pheochromocytoma (tumor of adrenal gland), POB inhibits alpha1 and alpha2, negative feedback by alpha2 blocked, POB lowers blood pressure by inhibiting alpha1 but NE and Epi can act on beta2 to increase blood pressure
Control of the eye
Eye is under sympathetic and parasympathetic control, iris circular muscle (M3), iris radial muscle (alpha1)
Control of ciliary body
Ciliary body under sympathetic and parasympathetic control, ciliary epithelium (beta1), ciliary muscle (M3)
Beta1 receptors in eye
Facilitates aqueous humor secretion
Alpha1 receptors in the eye
Reduces aqueous humor production
M3 receptors in the eye
Mediates ciliary muscle contraction, accommodation of focus for near vision, tenses and opens pores in trabecular meshwork to facilitate aqeuous humor outflow
Glaucoma
Damage to optic nerve due to buildup of intraocular pressure inside the eye
Aqueous humor exit
Exits through the canal of Schlemm through the trabecular meshwork, if aqueous humor builds up it can cause glaucoma
