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)

To investigate the participation of neuropeptides present in the peripheral endings of primary afferent neurons in the inflammatory response, immunoreactive substance P (iSP), calcitonin gene-related peptide (iCGRP) and neurokinin A (iNKA) levels in the s.c. perfusate, and inflammatory response (edema and plasma protein extravasation) evoked in rat paw by noxious stimulation were determined. The effects of these peptides on plasma protein extravasation in the skin of the hind paw of mice were also examined with the pontamine sky blue protein labelling method. The following results were obtained. 1) Immersion of the rat hind paw for 30 min into hot water adjusted to 47 degrees C led to a marked increase in the release of iSP and iCGRP in the subcutaneous perfusate with the formation of thermal edema. 2) Mechanical stimulation (600 g, 10 min) to the hind paw or electrical stimulation of the saphenous and sciatic nerves (10 V, 2 Hz, 1msec duration, 10 min) evoked the increase of iSP release in the perfusate with plasma protein extravasation. 3) iNKA release was not affected by neither heat nor mechanical stimulation. 4) Intraplantar injection of SP, CGRP and NKA induced plasma protein extravasation, the order of potencies being SP greater than CGRP greater than NKA. The action of SP was antagonized by spantide, an SP antagonist. The injection of CGRP with SP produced a synergistic action on plasma protein extravasation. 5) Neonatal pretreatment with capsaicin, which is known to degenerate small-diameter primary afferent neurons, caused the decrease in amount of iSP and iCGRP released during noxious heat stimulation. 6) Pretreatment with Compound 48/80, or stem bromelain and emorphazone, or des-Arg9-[Leu8]-BK, inhibited the iSP release evoked by noxious heat stimulation. 7) Opioids such as morphine (mu-agonist) and ethylketocyclazocine (kappa agonist) inhibited the heat stimulus-evoked iSP release and thermal edema, and the inhibitory effects were antagonized by pretreatment with their antagonists. 8) Morphine or ethylketocyclazocine or [D-Ala2,D-Leu5]-enkephalin (delta-agonist) inhibited the release of iSP evoked by electrical stimulation of the saphenous and sciatic nerves. These results indicate that SP and CGRP present in peripheral endings of small-diameter primary afferent neurons play an important role in the inflammatory response, and that opioids are involved in the regulation of inflammatory response through the inhibition of SP release.
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PMID:[A pharmacological study of the participation of the peripheral endings of primary afferent neurons in the inflammatory response evoked by heat and mechanical noxious stimulation]. 172 88

To investigate a physiological function of substance P (SP) present in the peripheral ending of sensory neurons, we determined immunoreactive SP (iSP) levels in the s.c. perfusate and the amount of edema evoked in rat paw by noxious heat stimulation. We found that immersion of rat paw into hot water (47 degrees C) for 30 min led to a significant increase of iSP in the perfusate and about 50% increase in paw volume. Neonatal pretreatment with capsaicin inhibited significantly the increase in both iSP and paw volume evoked by noxious heat stimulation. Acute and chronic denervation of the sciatic and saphenous nerves also inhibited the heat-evoked iSP release and edema remarkably. Intraplantar injection of SP evoked an increase in paw volume in dose-dependent manner. This increasing effect of SP on paw volume was more substantial than that produced by histamine. Simultaneous treatment with stem bromelain and emorfazone decreased significantly the heat-evoked iSP release and edema. These results suggest that 1) SP produced by noxious heat stimulation in the periphery may be released from the afferent fibers with small-diameter, 2) bradykinin may intervene in this SP release and 3) SP released in the periphery may be closely related to the edema formation of the thermal injury reaction.
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PMID:Contribution of substance P to heat-induced edema in rat paw. 244 42

The effects of bromelain were examined in rats with subcutaneous carrageenin-induced inflammation. After oral in vivo administration, bromelain (10 and 20 mg/kg p.o.) induced a significant decrease of both PGE(2) and substance P concentrations in the exudate. When added to the inflammatory exudate in vitro, the drug (25, 50, 100 microg/ml) did not affect PGE(2) concentrations and induced an increase in the substance P levels. Our data indicate that bromelain reduces the production of two key mediators of inflammation. This effect does not seem to be related to a direct action of the drug on PGE(2) and SP released in the exudate in response to the inflammatory stimulus.
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PMID:In vivo and in vitro effects of bromelain on PGE(2) and SP concentrations in the inflammatory exudate in rats. 1193 78