Nicotinic Cholinergic Receptors First efferent receptor outside CNS Acetylcholine is the pre-synaptic neurotransmitter N M (Nicotinic-Muscle) receptor for skeletal muscle “Neuromuscular blockers” block the N M receptor N N (Nicotinic-Nerve) receptor for ganglia “Ganglionic blockers” block the N N receptor Receptor activation opens sodium channels Generates action potential in postsynaptic muscle Generates EPSP in postsynaptic neurons
Muscarinic Receptors Receptors for post-ganglionic receptors All parasympathetic Few sympathetic Five major subclasses, M1 thru M5 M1, M4 and M5 are mostly in CNS The heart is mostly M2 M2 is an inhibitory receptor Acts by reducing cyclic AMP Most glands & smooth muscle have M3 M3 is an excitatory receptor Acts by increasing calcium Other types of receptors may be present
Muscarinic Synapse Ach Ach Receptor Choline + Acetate Post synaptic Heart (M 2 receptor) Or Gland/Smooth Muscle (M 3 ) Reuptake Ach + Ach Esterase G Protein cyclic AMP (M 2 ) Calcium (M 3 ) Diet AchE Inhibitors Muscarinic Blockers Muscarine & other Agonists
Parasympathetic Drugs Parasympatholytics Suppress parasympathetic activity Antagonists, specific to general ganglionic, neuromuscular (nicotinic cholinergic) M1 thru M5 (muscarinic cholinergic) Parasympathomimetics Enhance parasympathathetic activity Cholinesterase inhibitors Agonists Specificity, as with antagonists
Sympathetics Cholinergic synapse at ganglia : Acetylcholine (ACh) is neurotransmitter Nicotinic cholinergic receptors on postganglionic cell body membrane Adrenergic synapse at target organ : Norepinephrine (NE; noradrenalin) is neurotransmitter Acetylcholine ( sympathetic [muscarinic] cholinergic ) receptors on sweat gland cells.
Adrenergic Receptors Norepinephrine binds to 2 classes of receptors alpha adrenergic receptors Typically excitatory beta adrenergic receptors Typically inhibitory Sympathetic Adrenergic Receptors: receptors & receptors Function by means of 2nd messengers α 1 increases calcium α 2 reduces cyclic AMP β receptors increase cyclic AMP
Adrenergic Synapse N.E. N.E, Receptor Post synaptic 1 , 2 (smooth muscle) 1 (Heart) 2 (smooth muscle) or 3 (adipocytes) Reuptake + G Protein L-DOPA Dopamine N.E. N.E. cyclic AMP ( ) cyclic AMP ( 2 ) Calcium ( 1 ) COMT & MAO Homovanillic Acid (HVA) uptake Urine N.E. Adrenergic Blockers Adrenergic Agonists MAO or COMT Inhibitors Reserpine
Adrenergic Receptors Alpha Receptors Norepinephrine has high affinity for alpha receptors Epinephrine has lower affinity for alpha receptors Alpha 1 receptors increase calcium This is usually stimulatory sub-subclasses: 1A 1B 1C Alpha 2 receptors reduce cyclic AMP This may be stimulatory or inhibitory, depending on the cell type sub-subclasses: 2A 2B 2C
Adrenergic Receptors Beta Receptors Epinephrine & N.E. have high affinity for beta receptors Beta receptors increase cyclic AMP This may be stimulatory or inhibitory, depending on the cell type
Adrenal Medulla Chromaffin cells of adrenal medulla act like “postganglionic sympathetics”. Have nicotinic cholinergic receptors on cell bodies Release catecholamines: epinephrine (~80%), norepinephrine (~20%), dopamine (trace) Systemic effects: similar to activation of the sympathetic nervous system.
“ Fight or Flight” Sympathetic Defense Response Increased arterial pressure Increased heart rate and contractility Increased blood flow to skeletal muscles Decreased blood flow to GI tract Increased cellular metabolism Increased glycogenolysis and blood glucose Increased pupil diameter/lens flattening