Nerve-ending associated enzymes

Schematic illustration of a generalized cholinergic junction (not to scale). 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 -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. 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 (see text). This step can he blocked by botulinum toxin. Acetylcholine s action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending modulate transmitter release. SNAPs, synaptosome-associated proteins VAMPs, vesicle-associated membrane proteins.

The cell damage associated with inflammation acts on cell membranes to cause leukocytes to release lysosomal enzymes arachidonic acid is then liberated from precursor compounds, and various eicosanoids are synthesized. As discussed in Chapter 18, the cyclooxygenase (COX) pathway of arachidonate metabolism produces prostaglandins, which have a variety of effects on blood vessels, on nerve endings, and on cells involved in inflammation. The lipoxygenase pathway of arachidonate metabolism yields leukotrienes, which have a powerful chemotactic effect on eosinophils, neutrophils, and macrophages and promote bronchoconstriction and alterations in vascular permeability. 

Gangliosides and Associated Enzymes at the Nerve-Ending Membranes... 

Documented effects The alkaloid protopine (fumarine) caused narcosis in amphibians and, in mammals, caused paralysis of sensory nerve endings and increased reflex excitability. The alkaloid slightly increased the effects of analeptics and induced catalepsy (Chen-Gu 1957 Cheney 1963). In acute experiments with animals under narcosis, reduced heart rate and increased heartbeat amplitude occurred and, for a short time, decreased blood pressure was observed. Protopine has antiarrhythmic action with better effects than novocainamide and quinidine (Sadritdinov and Kurmukov 1980). In a screen to determine effects on platelet aggregation, extracts of this species showed complete inhibition of aggregation. This result was found to be caused by protopine (Sener 1994). Extracts of the dried plant displayed high rates of inhibition against the enzymes acetylcholinesterase and butyrylcholinesterase, which are associated with Alzheimer s disease (Orhan et al. 2004). 

COMT activity has been demonstrated in many tissues of the body in almost all cases it appears to be a cytoplasmic enzyme. However, in adipose tissue and erythro< es some enzyme activity is associate with the cell-membranes. In sympathetically innervated tissues most of the COMT activity is located in cells other than the adrenergic neurons (extraneuronal). Recent evidence sug ts. however, that small amounts of COMT are also present in adrenergic nerves. In the brain considerable amounts of COMT are recovered in fractions containing nerve endings (synaptosomes), suggesting a partially neuronal location of the en me in this organ. 

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