Tachykinins degradation

We will first consider the synthesis, release and localization of tachykinins in the airways. Next we will examine the impact of tachykinin degradation and tachykinin receptor expression on the physiological actions of these neurotransmitters in the airways. Finally, we will review the evidence for modulation of the effects of tachykinins in the inflammatory microenvironment (e.g. in asthma) and we will describe the interactions of tachykinins with mast cells and lymphocytes. 

The tachykinins are sometimes thought to act as a unit in some areas of the nervous system, because (1) SP and NKA are produced from a common precursor, (2) the processing of the pre-proprotein involves the same proteolytic enzymes, (3) different tachykinins can be stored and co-released from the same neuron, (4) they are degraded by the same enzymes, and (5) different peptides may activate the same receptors (Hokfelt et al. 2001). However, the distribution and expression levels of the various PPTs and NK receptors are quite distinct in many brain regions. 

Endopeptidase-24.II (EC 3.4.24.11 NELP neutral endopeptidase neprilysin, enkephalinase) is a zinc-metalloproteinase, found both in soluble and plasma membrane forms. It is an important enzyme in neuropeptide degradation. Notable neuropeptide substrates include tachykinins (substance P, neurokinin A, neurokinin B), endothelins (ET-1, ET-2, ET-3), atrial natriuretic peptide, neurotensin, somatostatin and cholecystokinins. 

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