Amidation Axonal

Both anandamide and 2-AG are inactivated by enzymatic hydrolysis (Goparaju et al. 1998). Fatty acid amide hydrolase (FAAH) is an enzyme that catalyses their hydrolysis. High concentrations of FAAH were found in the cerebellum, hippocampus and neocortex of rat brain, which are also rich in cannabinoid receptors. Further, there is a complementary pattern of distribution of FAAH and the CBl receptor. For example, in the cerebellum, FAAH is found in the cell bodies of Purkinje cells and the CBl receptor is found in the axons of granule cells and basket cells, which are presynaptic to Purkinje cells. 2-AG may also be inactivated by direct esterification into membrane phospholipids. Cannabinoid Receptors... 

Anandamide can be hydrolyzed to arachidonic acid and ethanolamine by fatty acid amide hydrolase (FAAH) (Cravatt et al., 1996 Wei et al., 2006) (Fig. 1). FAAH is highly expressed in the brain, where it is expressed at high concentrations in neuronal cell bodies and dendrites that are juxtaposed to axon terminals containing CB receptors. This suggests that anandamide hydrolysis occurs post-synaptically (Piomelli, 2003). 

The tachykinins are a family of small peptides (fewer than 50 residues), each of which has the same amino acid sequence, Phe-X-Gly-Leu-Met-NH2, at the amidated carboxy terminus (Fig. 7.1). Although three primary mammahan tachykinins - substance P, neurokinin A (NkA) and neurokinin B (NkB) - have been recognized, only substance P and NkA have been identified in the lungs and airways. Tachykinins are synthesized in nerve cell bodies, appropriately processed, and then transported by axoplasmic flow to the terminal ramifications of axon dendrites, where they serve their neurotransmitter functions. Both substance P and NkA are derived from transcription and translation of the preprotachykinin I (PPT-I) gene (Nawa et al., 1984 Krause etal., 1987). NkB is derived from a separate gene. 

The role of skin nerves in NIICRs has been studied using capsaicin (frfl s-8-methyl-N-vanillyl-6-nonen-amide), which is known to induce a release of bioactive peptides, such as substance P, from the axons of unmyelinated C-fibers of sensory nerves. Pretreatment of the skin with capsaicin inhibits erythema reactions in histamine prick tests (Bernstein et al. 1981), but does not inhibit either erythema or edema elicited by benzoic acid or methyl nicotinate (Larmi et al. 1989a). This suggests that NIICRs to these model substances are not a type of neurogenic inflammation of the skin. Topical anesthesia inhibits erythema reactions to histamine, benzoic acid and methyl nicotinate, but it is not known whether the inhibitory effect is due to the influence on the sensory nerves only or whether the anesthetic also affects other cell types or regulatory mechanisms of immediate-type skin inflammation (Larmi et al. 1989a). 

Boegman, R. j., and E. X. Albuquerque Axonal transport in rats rendered paraplegic following a single subarachnoid injection of either batrachotoxin or 6-aminonicotin-amide into the spinal cord. J. Neurobiol. 11, 283—290 (1980). 

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