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

1. The possibility that tachykinin NK1 receptors are involved in the plasma extravasation evoked by intradermal (i.d.) injection of Phoneutria nigriventer venom (PNV) in rat dorsal skin in vivo has been investigated. 2. Local oedema formation induced by the i.d. injection of test agents was measured by the extravascular accumulation of intravenously (i.v.) injected 125I-labelled human serum albumin over a 30 min period. 3. The tachykinin NK1 agonist, GR73632 (30 pmol per site), induced local oedema formation which was potentiated by co-injection with the neuropeptide vasodilator, calcitonin gene-related peptide (CGRP, 10 pmol per site). The non-peptide tachykinin NK1 receptor antagonist, SR140333 (0.03-1 nmol per site co-injected, i.d.) significantly inhibited (0.3 nmol per site, P < 0.05; 1 nmol per site, P < 0.001) local oedema formation induced by GR73632 with CGRP but not that induced by histamine (10 nmol per site) with CGRP. 4. PNV (0.03-0.3 microgram per site) injected i.d. induced dose-dependent local oedema formation. SR140333 (1 nmol per site, co-injected i.d.) inhibited oedema formation; with complete inhibition observed at doses of 0.03 microgram (P < 0.05) and 0.1 microgram (P < 0.001); and partial inhibition (50%) observed with the highest dose of PNV, 0.3 microgram (P < 0.05). 5. Local oedema formation induced by PNV was not affected by systemic pretreatment with the bradykinin B2 receptor antagonist, Hoe 140 (80 nmol kg-1, i.v.), which was used at a dose which significantly inhibited oedema formation by bradykinin (1 nmol per site). 6. Local oedema formation induced by PNV was significantly inhibited (P < 0.01) by co-injection of the histamine H1 receptor antagonist, mepyramine (2.5 nmol per site), together with the 5-hydroxytryptamine (5-HT) antagonist, methysergide (2.8 nmol per site). 7. In the presence of all three antagonists (mepyramine 2.5 nmol per site; methysergide, 2.8 nmol per site and SR140333 1 nmol per site), the plasma extravasation induced by PNV was further significantly inhibited (P < 0.001, when compared with PNV injected i.d. alone; P < 0.05 when compared with PNV co-injected with mepyramine and methysergide and P < 0.01, when compared with PNV co-injected with SR140333). 8. These results suggest that oedema formation evoked by i.d. PNV in rat skin may be partially mediated via a mechanism involving tachykinin NK1 receptors and that this effect is independent of histamine and 5-HT.
 ...
PMID:The effect of a tachykinin NK1 receptor antagonist, SR140333, on oedema formation induced in rat skin by venom from the Phoneutria nigriventer spider. 873 30

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.
 ...
PMID:Intraplantar injection of nerve growth factor into the rat hind paw: local edema and effects on thermal nociceptive threshold. 874 Jun 10