| How is cholinergic neurotransmission? | Ach neurotransmitter is seen in preganglionic fibers of ANS, postganglionic of parasympathetic, preganglionic fibers terminating in adrenal medulla.
Cholinergic neurons innrevate muscles of somatic system, play important role in CNS (Patients with Alzheimers have loss of cholinergic neurons in temporal lobe and entorhinal cortex, most drugs that treat diseases are Achesterase inhibitors)
It is in postganglionic for sympathetic varicosities innervating sweat glands in skin. |
| How is neurotransmission in cholinergic neuron? | Neurotransmission occurs in six steps:
Synthesis of Ach (choline transported from ECM to cytoplasm by energy-dependent carrier system that cotransports Na, cannot diffuse through membrane since + charge, can be inhibited by hemicholinium drug, uptake of choline is rate-limiting step of synthesis, then choline acetyl-transferase catalyzes rxn w/acetyle CoA to make acetylcholine)
Storage (packaged in presynaptic vesicles by active transport, vesicle contains ATP and proteoglycan, which are potential cotransmitters, vesilces are called varicosities along nerve terminal)
Release of Ach (Voltage gated Ca channels on presynaptic membrane open, causes increase in concentration of intracellular Ca promote fusion of vesicles with cell membrane are release of Ach, can be blocked by botulinum toxin, black widow spider venom can cause release of all Ach stored in synaptic vesicles to the space)
Binding to receptors (Binds postsynaptic receptors or presynaptic ones that released it, two classes postsynaptic Musc and Nic)
Degradation of Ach (Acetylecholinesterase cleaves Ach into choline and acetate in synaptic cleft, there is also pseudocholinesterase in plasma but no role
Recycling of choline (recaptured by Na-coupled transporters |
| How are muscarinic cholinergic receptors? | Bind Ach and recognize muscarine an alkaloid in poisonous mushrooms, weak affinity, five subclasses (M1, M2, M3, M4, M5) only 123 are functionally characterized.
Located on autonomic effector organs [heart, Smooth muscles, brain, exocrine], drugs usually act more on Ni receptors than these.
Mechanism of action is G-protein coupled receptor slow response excitatory or inhibitory, M1 and M3 induces Gq activates Phospholipase C, M2 induces Gi inhibit adenylyl cyclase |
| How are nicotinic cholinergic receptors? | Bind acetyl choline and recognize nicotine, weak affinity to muscarine, 5 subunits, ligand gated ion channels always cause rapid increase in cellular permeability to Na+ (depolarization) and Ca2+ (excitation)
Located in CNS, Adrenal medulla (NN), autonomic ganglia (NG), and neuromuscular jucntions (NM)
Those of autonomic ganglia differ from those of neuromuscular, ganglionic are blocked by hexamethonium whereas neuromuscular are blocked by tubocurarine. |
