Munir Gharaibeh, MD, PhD, MHPEmgharaib@ju.edu.jo

Sites of OriginsLength of Preganglionic and

Postganglionic neurons.Ratio of preganglionic:

postganglionic

FunctionFunctionSympatheticSympatheticParasympatheticParasympathetic

Heart rateHeart rateIncreasedIncreasedSlowedSlowed

Blood vesselsBlood vesselsConstrictedConstrictedDilatedDilated

Stomach and Stomach and intestineintestine

Decreased Decreased activity and activity and secretionssecretions

Increased Increased activity and activity and secretionssecretions

Salivary and Salivary and bronchial bronchial glandsglands

Decreased Decreased secretionsecretion

Increased Increased secretionsecretion

Urinary bladderUrinary bladderBody relaxed, Body relaxed, sphincter sphincter constrictedconstricted

Body Body contracted, contracted, sphincter sphincter relaxedrelaxed

Bronchial Bronchial musclemuscle

RelaxedRelaxedContractedContracted

Blood sugarBlood sugarRaisedRaised

EyeEyePupils dilatedPupils dilatedPupils Pupils constricted, constricted, accommodation accommodation for near visionfor near vision

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Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (ChT). This transporter can be inhibited by hemicholinium drugs.

In the cytoplasm, acetylcholine is synthesized from choline and acetyl Co-A (AcCoA) by the enzyme choline acetyltransferase (ChAT).

Acetylcholine is then transported into the storage vesicle by a second carrier, the vesicle-associated transporter (VAT), which can be inhibited by vesamicol.

Peptides (P), adenosine triphosphate (ATP), and proteoglycan are also stored in the vesicle.

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Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft. This step can be blocked by botulinum toxin.

Acetylcholine's action is terminated by metabolism by the enzyme acetylcholinesterase.

Receptors on the presynaptic nerve ending modulate transmitter release.

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ACh released from the motor nerve terminal interacts with subunits of the pentameric nicotinic receptor to open it, allowing Na+ influx to produce an excitatory postsynaptic potential (EPSP).

The EPSP depolarizes the muscle membrane, generating an action potential, and triggering contraction. Acetylcholinesterase (AChE) in the extracellular matrix hydrolyzes ACh.

The ENS receives input from both the sympathetic and the parasympathetic systems and sends afferent impulses to sympathetic ganglia and to the central nervous system.

Many transmitter or neuromodulator substances have been identified in the ENS.

AC: absorptive cellCM: circular muscle layerEC: enterochromaffin cellEN: excitatory neuronEPAN: extrinsic primary afferent neuronIN: inhibitory neuron IPAN: intrinsic primary afferent neuronLM: longitudinal muscle layer MP: myenteric plexusNP: neuropeptides SC: secretory cell SMP: submucosal plexus

Definition: Drugs which produce effects similar to

those observed during the stimulation of postganglionic parasympathetic nerve fibers or have actions similar to acetylcholine.

Choline Esters.Alkaloids.Cholinesterase Inhibitors or

Anticholinesterases.

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Choline Esters: Acetylcholine:▪ Naturally released ACh from the cholinergic nerve endings.▪ Very short acting because of rapid hydrolysis by AChase

enzyme.▪ Used only in experimentation.

Methacholine: used in in the diagnosis of cystic fibrosis and atropine poisoning.

Carbachol: not used clinically because of nicotinic activity

Bethanechol:▪ Synthetic, long acting, used orally or s.c..▪ Used in postoperative atony, when there is no obstruction.▪ Causes flushing, sweating, colic.

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Choline Esters.Alkaloids: produce similar actions to ACH but

inconsistent Muscarine: present in some species of

mushroom (Amanita muscaria), can cause poisoning.

Nicotine: Pilocarpine: not hydrolyzed by

cholinesterase, used topically in glaucoma.

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