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)

Substance P and somatostatin may be transmitters of nociceptive information, which are involved in the transmission of pressure and heat nociceptive information, respectively, in the spinal dorsal horn. Calcitonin gene-related peptide, which is present in the primary sensory neurons having substance P or somatostatin, may function as a pain-promoting substance and be involved in the production of inflammation-induced hyperalgesia. The descending noradrenergic system plays a role in inhibiting nociceptive transmission in the spinal dorsal horn, and inhibits the release of substance P evoked by noxious mechanical stimulation. Persistent noxious stimuli increase the release of Met-enkephalin from the nucleus reticularis gigantocellularis, which promotes the activity of the descending noradrenergic system. Morphine activates the descending noradrenergic system, acting on the nucleus reticularis gigantocellularis. Morphine also activates the descending serotonergic system, which inhibits the release of somatostatin evoked by thermal noxious stimulation.
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PMID:[Neuropeptide-mediated transmission of nociceptive information and its regulation. Novel mechanisms of analgesics]. 170 78

1. Opioids have been shown to inhibit substance P (SP) release from primary afferent neurones (PAN). In addition, opioid receptors have been identified on PAN of the vagus nerves. Sodium cromoglycate (SCG) decreases the excitability of C-fibres in the lung of the dog in vivo. We have utilised a multi-superfusion system to investigate the effect of opioids and SCG on the release of SP from the rat trachea in vitro. 2. Pretreatment of newborn rats with capsaicin (50 mg kg-1 s.c. at day 1 and 2 of life) resulted in a 93.2 +/- 6.3% reduction in tracheal substance P-like immunoreactivity (SP-LI) content when determined by radioimmunoassay in the adult. 3. Exposure to isotonically elevated potassium concentrations (37-90 mM), capsaicin (100 nM-10 microM), and bradykinin (BK; 10nm-1 microM) but not des-Arg9-BK (1 microM) stimulated SP-LI release by a calcium-dependent mechanism. 4. SCG (1 microM and 100 microM) did not affect spontaneous, potassium (60 mM)- or BK (1 microM)-stimulated SP-LI release. 5. Morphine (0.1-100 microM) caused dose-related inhibition of potassium (60 mM)-stimulated SP-LI release with the greatest inhibition of 60.4 +/- 13.7% at 100 microM. The effect of morphine was not mimicked by the kappa-opioid receptor agonist, U50,488H (10 microM) or the delta-opioid receptor agonist, Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE). 6. The effect of morphine was totally abolished by prior and concomitant exposure to naloxone (100 nM) which had no effect on control release values. 7. We conclude that opioid receptors, predominantly of the MM-opioid receptor subtype, inhibit SP-LI release from PAN in the rat trachea and suggest that centrally inactive MM-opioid receptor agonists may have therapeutic potential in the treatment of asthma.
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PMID:Morphine, but not sodium cromoglycate, modulates the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro. 171 4

Electric stimulation of the rat sciatic nerve containing sensory afferent fibers produced an increase in cutaneous blood flow. Morphine (10, 30 mumol.kg-1 ia infusion) inhibited the electric stimulation-induced increase of the cutaneous blood flow velocity, and its effect was antagonized by naloxone (2 mg.kg-1 ip). In order to investigate the cause of this effect, we determined immunoreactive substance P (iSP) levels in the sc perfusate of hind paw. We found that electric stimulation of the sciatic nerve led to a significant increase of iSP release into the sc perfusate. Morphine (30 mumol.kg-1 ia infusion) inhibited the electrical stimulation-induced release of iSP, and this effect was completely antagonized by naloxone (2 mg.kg-1 ip). These result suggest that morphine-induced inhibition of the electrical stimulation-evoked increase in cutaneous blood flow could result from inhibition of the release of SP from peripheral sensory nerve endings.
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PMID:[Effects of morphine on cutaneous blood flow and substance P release evoked by electric stimulation of rat sciatic nerve]. 172 70

A physiological role of substance P (SP) in inflammatory reaction was examined in the rat incisor pulp and inferior lip. SP content in pulps and lips significantly increased after antidromic stimulation of the inferior alveolar nerve. Following the same stimulation, vascular permeability also increased significantly in pulps and lips, and this permeability response was significantly inhibited by an SP-antagonist. Morphine reduced the permeability response to antidromic stimulation in pulps but had no effect in lips. N-methyl levallorphan (a peripherally selective narcotic antagonist) prevented the morphine-induced reduction, and was more potent than naloxone. Morphine caused a marked increase of SP content in pulps following antidromic stimulation of the inferior alveolar nerve but failed in lips. These suggest a possibility that a peripheral SP release-suppressive mechanism by opiates may exist in pulps but not in lips. The permeability response to antidromic stimulation was also reduced by aspirin and a bradykinin antagonist in both of the tissues, indicating that prostaglandin and bradykinin may be related to this response. Since mepyramine and methysergide inhibited the permeability response in lips but were inactive in pulps, there is a difference in participation of histamine and serotonin between the two tissues. SP injection into the dental pulp and lip induced dye leakage. This response was inhibited by compound 48/80 pretreatment in lips whereas it was resistant in pulps. Histamine content in lips decreased significantly after antidromic stimulation and compound 48/80 pretreatment, but it was not changed in pulps. The present results suggest that in lips after being released from the peripheral sensory nerve endings SP may act on vascular system through histamine release from mast cells, while in pulps SP may directly cause vascular response because mast cells may be few or not exist.
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PMID:[Role of substance P on neurogenic inflammation in the rat dental pulp and inferior lip]. 172 14

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

The effects of locally applied opioids on the release of immunoreactive Substance P (iSP), induced by mechanical stimuli, from the dorsal horn of the rabbit in situ, were investigated. Morphine and met-enkephalin (met-enk), but not dynorphin A (1-17) (DYN), in a concentration of 10 microM, significantly inhibited the evoked release. These inhibitory effects of morphine and met-enkephalin were antagonized by the local application of naloxone (10 microM) to the dorsal horn. These results suggest that the inhibition of the release of Substance P induced by noxious mechanical stimuli may be mediated by mu and delta, but not by kappa opioid receptors.
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PMID:Met-enkephalin and morphine but not dynorphin inhibit noxious stimuli-induced release of substance P from rabbit dorsal horn in situ. 241 Aug 7

Capsaicin given intravenously (i.v.) into the vena cava or intra-arterially (i.a.) into the aortic arch of anesthetized guinea-pigs induced dose-dependent increases in pulmonary-flow resistance (R) and dynamic thoracic elastance (E). Threshold doses were 0.5-1.0 micrograms/kg body weight; greater than 8.0 micrograms/kg induced tachyphylaxis. These responses to capsaicin, i.v. or i.a., were similar after decentralization, bilateral vagotomy, or glossopharyngealotomy, and after autonomic blockers (mecamylamine, atropine, mepyramine, and bethanidine). Morphine significantly reduced responses to capsaicin but had no effect on responses to substance P (SP). Naloxone did not reverse the inhibitory effect of morphine, and neither reduced nor enhanced capsaicin-induced increases. Of the two antagonists to SP examined (given i.v.), [D-Pro2,D-Trp7,9]SP had no effect on SP-induced increases but abolished capsaicin-induced increases in R, though without affecting increases in E, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP reduced increases in R induced by both SP and capsaicin but had no effect on increases in E. Capsaicin (2.0-32.0 micrograms/kg i.v. or i.a.) had no bronchospastic effect in guinea-pigs given this drug (50.0 mg/kg s.c.) 7 days earlier. We conclude that in guinea-pigs--unlike other species--capsaicin causes bronchospasm without stimulating any afferent receptors in a centrally mediated bronchospastic reflex arc.
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PMID:Does capsaicin cause reflex bronchospasm in guinea-pigs? 241 59

We studied whether morphine, norepinephrine (NE), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) inhibit the potassium-stimulated release of substance P (SP) from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2-cm segment of lumbosacral spinal cord was removed, chopped into 0.5 X 0.5 mm pieces, weighed, placed in a perfusion chamber and perfused at 37 degrees C with a modified Krebs bicarbonate buffer. Perfusate was collected, lyophilized, then assayed for SP using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl for 8 min produced a calcium-dependent increase in the release of SP from a basal level of approximately 0.1 pg/mg tissue/min to 0.3 pg/mg tissue/min. Morphine and NE at concentrations of 10(-4) and 10(-5) M did not alter basal release but caused a significant reduction in the potassium-stimulated release of SP. Naloxone (10(-5) M) and phentolamine (10(-5) M) did not affect SP release but attenuated the effects of morphine and NE, respectively. Naloxone did not antagonize the inhibition of release produced by NE nor did phentolamine block the effect of morphine, suggesting that the actions of the agonists are independent. In contrast, 5-HT and GABA at concentrations of 10(-4) M and 10(-5) M did not significantly alter the basal or potassium-stimulated release of SP. These results demonstrate a differential regulation of SP release in the spinal cord and support the hypothesis that morphine and NE may modify nociception, in part, by inhibiting the release of SP in the spinal cord.
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PMID:Morphine and norepinephrine but not 5-hydroxytryptamine and gamma-aminobutyric acid inhibit the potassium-stimulated release of substance P from rat spinal cord slices. 242 94

The present study was aimed to examine possible influences of bradykinin (BK) and substance P (SP) on met-enkephalin (ME)-like peptide content in the rat incisor pulp. Des-Arg9-[Leu8]-BK, a potent BK-antagonist, significantly reduced the increased content of ME-like peptides induced by noxious stimulation, while the effect of BK-antagonist was reversed in combination with BK. Morphine decreased the increased content of ME-like peptides. Ethylketocyclazocine, a kappa-agonist, also decreased the increased content of the peptides. From these results, it was suggested that BK might be a trigger in the increase of ME-like peptide content induced by noxious stimulation and, in contrast, ME-like peptides in the pulp might inhibit BK release from the pulp in a negative feedback mechanism. On the other hand, [D-Pro2,D-Trp7,9]-SP, a potent SP-antagonist, did not show any significant influence to ME-like peptide content in the pulp. Furthermore, the content was not changed following cutting of inferior alveolar nerve. From these results, it was suggested that ME-like peptides in the pulp cells might be independent on SP-containing nerves in the pulp.
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PMID:Influences of bradykinin and substance P on the met-enkephalin-like peptide content in the rat incisor pulp. 242 25

Dorsal and ventral root depolarizing responses to capsaicin (1 microM) and substance P (SP; 1 microM) were measured from the isolated, hemisected spinal cord of the neonatal rat. Capsaicin depolarized the dorsal and ventral roots. The mechanism of ventral root depolarization was presynaptic; since dorsal root depolarization preceded the ventral, and the ventral depolarization was eliminated when synaptic transmission was blocked in the absence of calcium. SP depolarized the ventral root without affecting the dorsal root. The SP-induced depolarization of the ventral root was reduced but not abolished by blocking synaptic transmission with low calcium, suggesting that SP acted postsynaptically on motoneurons and excitatory interneurons to depolarize the ventral root. Morphine (10 microM) abolished the capsaicin-induced ventral root depolarization, but only slightly suppressed the SP response (30%). The capsaicin-induced depolarization of the ventral root was enhanced greatly (238%) when morphine, which had been in the superfusion for 1 h, was removed and naloxone (1 microM) was added to the superfusion solution, whereas the SP response was not augmented during withdrawal from acute morphine. Furthermore, a putative SP antagonist ([D-Arg1, D-Pro2, D-Tryp7,9, Leu11]-SP) prevented the augmented capsaicin ventral root response during precipitated withdrawal. These data provide electrophysiological evidence for a presynaptic mechanism of acute morphine withdrawal in the neonatal rat spinal cord.
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PMID:Electrophysiological evidence for a presynaptic mechanism of morphine withdrawal in the neonatal rat spinal cord. 242 42


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