Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phospholipase A2 is ubiquitous in nature, with the highest concentrations occurring in pancreatic juice and in the venom of snakes. Local oedema formation is a common feature of the effects caused by snakebite, and indicates an increase in vascular permeability that could be produced by lipid mediators such as lysophospholipids, eicosanoids or PAF release by the enzymatic activity of PLA2. Desalted porcine pancreatic PLA2 exhibited strong oedema-inducing activity in a similar form to PLA2 venom from Naja naja or Crotalus durissus terrificus. Furthermore, all three PLA2S caused the release of histamine from rat peritoneal mast cells. However, non-desalted pancreatic PLA2 that was presented as an ammonium sulphate suspension (3.2 M) had no proinflammatory activity and clearly did not release histamine in vitro. When the enzymatic activity of PLA2 on mast cell membranes prelabelled with [3H] arachidonic acid was determined, a relationship between the enzymatic activity and mast cell degranulation and the minimum oedema dose was observed. However, non-desalted porcine pancreatic PLA2 had the same enzymatic activity as the desalted enzyme but had little proinflammatory activity. This may be due to decreased histamine secretion caused by the presence of ammonium sulphate. Our study supports the idea that the proinflammatory activity of extracellular phospholipases could depend on their ability to cause mast cell degranulation. Moreover, the biological effects of PLA2 are correlated with the specific activities of the enzymes.
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PMID:Oedema formation and degranulation of mast cells by phospholipase A2 purified from porcine pancreas and snake venoms. 821 47

Nerve growth factor (NGF) is known to produce hyperalgesia as well as to stimulate synthesis of neuropeptides in dorsal root ganglia (DRG). In the present study, we wanted to determine the effects of local NGF administration and assess to which extent mast cell-dependent factors are mediating NGF responses. Rats received 1 daily unilateral intraplantar injection for 3 days. Local edema (days 1-3), changes in thermal nociceptive threshold (days 1-4), and the content of calcitonin gene-related peptide (CGRP) and substance P (SP) in the sciatic nerve (day 4), were determined. NGF injection caused edema which was absent in rats pretreated with compound 48/80 as well as in rats treated neonatally with capsaicin ('capsaicin denervation'). NGF-induced edema was not reduced by the neurokinin-1 receptor antagonist SR140333, but attenuated by the CGRP receptor antagonist CGRP[8-37]. On each day, NGF injection caused a decrease in thermal nociceptive threshold which lasted for less than 3 h. Capsaicin denervation, but not treatment with indomethacin, abolished NGF-induced thermal hyperalgesia. Treatment with compound 48/80 attenuated hyperalgesia produced by the first, but not by subsequent, NGF injections. On day 4, 24 h after the last of 3 NGF injections, thermal nociceptive threshold was not different from control values, but at that time, CGRP and SP were elevated in the sciatic nerve. We suggest therefore that NGF-induced local edema was caused by mast cell-derived vasoactive compounds which act together with afferent neuron-derived CGRP to increase vascular permeability. NGF-induced thermal hyperalgesia most likely was caused by an increased sensitivity of peripheral endings of capsaicin sensitive afferents. This effect of NGF was not mediated by products of the cyclooxygenase pathway, and was also observed in mast cell-depleted rats.
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PMID:Intraplantar injection of nerve growth factor into the rat hind paw: local edema and effects on thermal nociceptive threshold. 874 Jun 10