Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvillar membranes derived from the brush border of the renal proximal tubule are very rich in peptidases. Pig kidney microvilli contain endopeptidase-24.11 associated with a battery of exopeptidases. The manner by which some neuropeptides are degraded by the combined attack of the peptidases of this membrane has been investigated. The contribution of individual peptidases was assessed by including inhibitors (phosphoramidon, captopril, amastatin and di-isopropyl fluorophosphate) with the membrane fraction when incubated with the peptides. Substance P, bradykinin and angiotensins I, II and III and insulin B-chain were rapidly hydrolysed by kidney microvilli. Oxytocin was hydrolysed much more slowly, but no products were detected from [Arg8]vasopressin or insulin under the conditions used for other peptides. The peptide bonds hydrolysed were identified and the contributions of the different peptidases were quantified. For each of the susceptible peptides, the main contribution came from endopeptidase-24.11 (inhibited by phosphoramidon). Peptidyl dipeptidase A (angiotensin-I-converting enzyme) was of less importance, even in respect of angiotensin I and bradykinin. When [2,3-Pro3,4-3H]bradykinin was also investigated at a lower concentration (20 nM), the conclusions in regard to the contributions of the two peptidases were unchanged. The possibility that endopeptidase-24.11 might attack within the six-residue disulphide-bridged rings of oxytocin and vasopressin was examined by dansyl(5-dimethylaminonaphthalene-1-sulphonyl)ation and by reduction and carboxymethylation of the products after incubation. Additional peptides were only observed after prolonged incubation, consistent with hydrolysis at the Tyr2-Ile3 and Tyr2-Phe3 bonds respectively. These results show that a range of neuropeptides are efficiently degraded by microvillar membranes and that endopeptidase-24.11 plays a key role in this process.
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PMID:Metabolism of neuropeptides. Hydrolysis of the angiotensins, bradykinin, substance P and oxytocin by pig kidney microvillar membranes. 243 10

Angiotensin-converting enzyme (CE) occurs in three types of cell: endothelial, epithelial, and neuroepithelial. In all three, it appears to be bound to plasma membrane. With antisera to the human enzyme, CE is demonstrated in paraffin sections on the apical surface of epithelial cells in the proximal tubule of the kidney, the mucosa of the small intestine, the syncytial trophoblast of the placenta, and the choroid plexus. Epithelial CE is characteristically found on microvillous surfaces in contact with an effluent, well placed to act on substrate in flux. In the brain, CE occurs in nerve fibers and terminals, mainly mesiobasally and in basal ganglia. Mesiobasal CE coincides with other components of the renin-angiotensin system (RAS) in the choroid/ventricular fluid, the subfornical organ, and the magnocellular neurosecretory system of the hypothalamus. Extrapyramidal CE, however, may not be related to the RAS. In the substantia nigra and the globus pallidus, the enzyme has the same cellular distribution as two putative neuromodulators, substance P and enkephalin, the latter a known substrate of CE.
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PMID:Angiotensin-converting enzyme in epithelial and neuroepithelial cells. 631 Apr 27

Substance P is a neuropeptide found principally in the central nervous system and peripheral afferent nerve fibers. It is widely distributed in the body, and its local release is thought to have important effects in the normal physiology and pathophysiology of several organ systems. Substance P releases histamine from mast cells and nitric oxide from endothelial cells. Systemic infusion of substance P causes a brisk natriuresis. Previously, proximal tubule transport in the kidney was measured in vivo during the infusion of substance P. Transport was inhibited. This could have been a direct action of substance P or secondary to the release of histamine or nitric oxide. Therefore, we have now studied the effect of substance P on isolated proximal tubules perfused in vitro. We found that 10(-10) M substance P caused a 50% reduction in the rate of fluid absorption in rabbit proximal straight tubule. This effect was reversible on removal of substance P from the bath. Inhibition of nitric oxide production with NG-monomethyl-L-arginine (10(-4) M) did not influence the action of substance P at 10(-10) M. The sensitivity of the proximal tubule to low concentrations of substance P, together with the recent findings of substance P-containing afferent fibers within the cortex of the kidney, suggest a role for substance P in the control of proximal tubule reabsorption, particularly in pathophysiological conditions associated with increased afferent nerve activity, such as ureteric occlusion.
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PMID:Substance P decreases fluid absorption in the renal proximal tubule. 917 29