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)

Cats were used as models of traumatic spinal cord injury. Each experimental animal received a 500 g-cm force to the exposed dura at the level of thoracic fourth vertebra. Somatosensory evoked potentials (SEPs), carotid arterial blood pressure (BP), and abdominal aorta blood flow in the treated groups were compared with those of the control group. The three treated groups received naloxone (5 mg/kg), TRH (5 mg/kg), and a combination of methyl-prednisolone sodium succinate (MP, 35 mg/kg) and epsilon-aminocaproic acid (EACA, 350 mg/kg). The SEPs which were done only in the naloxone treated group approached "normalcy" 24-26 hours after trauma as compared with the absence of SEPs in traumatized untreated group. In all three groups, the treatment increased the blood flow in abdominal aorta significantly. Morphine sulfate increased substance P (SP) immunoreactivity in the dorsal and ventral gray matter. Naloxone not only reversed this effect, it depleted SP below the saline control level. In order to establish that lipid free radicals are responsible for damage to biological membranes, their effects were also investigated in vitro: 14C-GABA uptake by mouse cortical slices which had decreased by 33% in the presence of superoxide (. O-2) generating system, horseradish peroxidase (HRP), was reduced only by 9% when superoxide dismutase was added to the medium. The latter also protected the nerve endings from damage by (. O-2) as examined by electron microscopy. It is concluded that the agents used in this study produce their ameliorating effects by virtue of their anti-inflammatory, anti-oxidant, and membrane stabilizing properties in addition to their effect on enhancing the regional microcirculation. The release of SP by naloxone may be responsible for the increase in blood flow. The consequences of traumatic injury as depicted in Fig. 1 are discussed at length.
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PMID:Prevention of damage in acute spinal cord injury by peptides and pharmacologic agents. 618 89

In chloralose-anaesthetized cats the iontophoretic application of substance P produced an excitation of dorsal horn nociceptive units, as found in earlier studies. Naloxone (0.1-0.2 mg/kg, IV) failed to abolish this response to substance P in any of the 9 cats studied. In 4 additional cats nociceptive units were tested with morphine (1.0-3.2 mg/kg, IV) and substance P in case the antinociceptive effect of descending pathways is mediated via an excitatory action, but in each case morphine and substance P produced opposite effects (depression and excitation, respectively), suggesting that this was not the case. The present results fail to support a naloxone-antagonizable inhibitory effect of substance P in the spinal cord.
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PMID:Naloxone fails to block substance P-induced excitation of spinal nociceptive units. 619 44

Tissue levels of substance P (SP) were determined by radioimmunoassay in cat dental pulps after unilateral electrical stimulation of the inferior alveolar nerve. Nerve stimulation (10 V, 10 Hz, 5 ms for 3 min) reduced the SP level at the stimulated side by approximately 40%, indicating a release of SP. Stimulation performed after infusion of morphine (0.3 mg/kg/min, i.v.) for 10 min did not reduce the pulpal SP-level. Naloxone (3 mg/kg, i.v.) administered immediately before the morphine infusion in three experiments, did not influence the effect of morphine on pulpal SP levels after nerve stimulation. This may indicate an action of morphine on a naloxone-insensitive receptor type. Morphine in the dosage used did not influence the intradental sensory nerve conductivity. The results indicate that morphine is able to inhibit stimulus evoked release of SP from peripheral endings of primary afferent neurons.
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PMID:Morphine inhibits substance P release from peripheral sensory nerve endings. 619 85

Approximately 5 segments of lumbo-thoracic spinal cord together with connected dorsal root ganglia were removed from 1-11-day-old rats and maintained in vitro. Dorsal root afferents, recorded from the ganglion and stimulated at the root entry zone, had conduction velocities typical of unmyelinated fibers (less than 2 m/s). The spinal terminals of individual afferents showed increased excitability with bath application of substance P and serotonin and decreased excitability with morphine sulfate, [D-ala2]methionine-enkephalinamide, manganese ions and magnesium ions. Naloxone by itself elicited no change in excitability, although it appeared to reduce the ongoing effect of opiates. Neurons recorded extracellularly in the dorsal horn responded to afferent volleys with one or more of 3 distinct phases: an excitation roughly coincident with the volley's arrival, a 50-300 ms period of inhibition, and a late excitation of 150-300 ms latency. The excitability results are accounted for by a model in which substance P, gamma-aminobutyric acid and possibly other depolarizing agents are contained in interneurons which synapse on afferent terminals. These interneurons could receive inhibitory enkephalinergic input, and, in the neonate but not the adult, excitatory serotoninergic input. An alternate scheme would have enkephalin and serotonin acting directly on afferent terminals, although perhaps by non-synaptic diffusion since the appropriate synapses have not been seen in histochemical studies. Such an action for enkephalin might explain the existence of opiate receptor on afferent terminals. The interneuronal responses to afferent volleys are parallel in most aspects to those found in the dorsal horns of adult mammals in vivo.
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PMID:Actions of opiates, substance P, and serotonin on the excitability of primary afferent terminals and observations on interneuronal activity in the neonatal rat's dorsal horn in vitro. 619 76

The addition of 50 mM K+ to the perfusate of cat hypothalamic slices results in a 3.4- and 5.5-fold increase in the levels of cholecystokinin (CCK) and substance P (sP) like immunoreactivity, respectively. The addition of morphine (10(-11)-10(-8) M; a mu receptor agonist) and D-Ala2-D-Leu5-enkephalin (DADL: 10(-12)-10(-10) M; a delta receptor agonist) resulted in a dose-dependent suppression of the K+-evoked release. SKF10047 (a sigma receptor ligand) and U50488H (a kappa receptor ligand) had no effect in doses up to 10(-6) M. Naloxone added with the lowest dose of agonist producing a maximal inhibition produced a dose-dependent reversal of the anti-release effects of morphine and DADL. The IC50 of naloxone for the antagonism by DADL and morphine of the release of CCK were similar, whereas the naloxone IC50 was lower for morphine than DADL in the reversal of the effects of the agonist in sP release. Within the constraints of receptor selectivity of the several ligands, these data suggest that at least two populations of opioid receptors (mu and delta) may be discriminated which govern the release of hypothalamic sP.
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PMID:Studies on the opiate receptor-mediated inhibition of K+-stimulated cholecystokinin and substance P release from cat hypothalamus in vitro. 619 38

The release of immunoreactive substance P (I-SP) from the myenteric plexus of the isolated guinea-pig small intestine and some of its characteristics have been investigated. Depolarizing stimuli, i.e. elevation of the extracellular K+ concentration or electrical field stimulation, increased the release of I-SP, the extent of the increase being dependent on the strength of the stimulus. Omission of Ca2+ from the bath medium prevented the stimulus-induced release of I-SP. Tetrodotoxin inhibited only the increase in I-SP release brought about by electrical stimulation but not that caused by elevated K+ concentrations. Gel exclusion chromatography on Sephadex G-25 showed that all the I-SP released by depolarization was co-eluted with authentic substance P. The methionine enkephalin analogue FK 33-824 significantly reduced the stimulus-induced release of I-SP, an effect that was prevented by the opiate antagonist naloxone. Naloxone alone significantly enhanced the stimulus-induced release of I-SP, which suggests that endogenously released opioid peptides also exert an inhibitory action on myenteric substance P-containing neurons. Putative excitatory neurotransmitters of the myenteric plexus, such as acetylcholine, bombesin, cholecystokinin octapeptide, and neurotensin, stimulated the release of I-SP in a tetrodotoxin-sensitive manner, whereas 5-hydroxytryptamine seemed ineffective. Capsaicin, known to release substance P from sensory neurons, also failed to alter the release of I-SP. The finding of a Ca2+-dependent release of I-SP caused by depolarizing stimuli further supports the concept that substance P is a neurotransmitter within the myenteric plexus. The activity of myenteric substance P-containing neurons appears to be controlled by a number of other putative enteric neurotransmitters.
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PMID:Characterization of the stimulus-induced release of immunoreactive substance P from the myenteric plexus of the guinea-pig small intestine. 620 63

Male Wistar rats were treated with pethidine (PT) or fentanyl (FN) subcutaneously (sc) followed by intrathecal (ith) non analgesic doses of methionine- (MENK) or leucine-enkephalin (LENK), neurotensin, (NT), substance P (SP) or cholecystokinin octapeptide 26-33 (CCK-8). Then the antinociceptive effect was measured during 1 h using tail-immersion test. LENK potentiated strongly PT and FN analgesia. MENK antagonized PT analgesia only transiently 30 min after administration and transiently potentiated FN analgesia. SP and CCK-8 potentiated significantly PT analgesia, whereas NT acted biphasically: increasing and then decreasing PT analgesia. SP, CCK-8 and NT augmented FN analgesia. Naloxone inhibited analgesia elicited by the studied opioids and neuropeptides. These data show that LENK affects similarly the analgesic effects of both studied opioids, whereas MENK acted differently on PT and FN analgesia. This may suggest that individual enkephalins have different pharmacological features when interacting with different analgesics. Also NT interacted differently with pethidine and fentanyl.
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PMID:Pharmacological interaction between neuropeptides and pethidine or fentanyl in rat spinal cord. 751 84

The peptide NK1-receptor antagonists, sendide and [D-Trp7]sendide, have been evaluated for antinociceptive activity in the capsaicin test. Both peptides, injected intrathecally (i.t.) 5 min prior to intraplantar capsaicin, produced a dose-dependent reduction of the capsaicin-induced paw licking response. Naloxone (4.0 mg/kg) pretreatment did not affect sendide- and [D-Trp7]sendide-induced antinociception, whereas naloxone at a dose of 0.5 mg/kg antagonized the antinociceptive effect of i.t. administered morphine. Conversely, the antinociceptive action induced by both NK1-receptor antagonists was reduced significantly by i.t. co-administration of substance P. Morphine-induced antinociception was not antagonized by co-administration of substance P. These results led us to the understanding of differential action mechanism of NK1-receptor antagonist- and morphine-induced antinociception as assayed by the capsaicin test.
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PMID:Differential antinociceptive effects of sendide, a NK1-receptor antagonist, and morphine in the capsaicin test. 752 10

Using alpha-chloralose-anesthetized cats, we studied blood pressure and heart rate responses to static contraction and passive stretch of the triceps surae muscle before and after microdialyzing the mu-opioid agonist [D-Ala2]-methionine enkephalinamide (DAME, 200 mumol/L) into the L-7 dorsal horn of the spinal cord. In addition, we measured contraction-induced substance P release in the dorsal horn before and after drug delivery. After 92 +/- 3 minutes of dialyzing the opioid agonist, contraction-induced increases in mean arterial pressure and heart rate were attenuated from control values of 58 +/- 7 mm Hg and 17 +/- 3 beats per minute to postdrug values of 27 +/- 7 mm Hg and 10 +/- 2 beats per minute, respectively. A similar attenuation was observed for the passive muscle stretches after 97 +/- 5 minutes of dialysis (control, 38 +/- 4 mm Hg and 8 +/- 2 beats per minute; after drug, 23 +/- 4 mm Hg and 5 +/- 1 beats per minute). Prior microdialysis of naloxone (300 mumol/L), a mu-antagonist, blocked this effect, suggesting that the opioid agonist has a specific receptor action. Naloxone alone had no effect on the pressor or tachycardiac responses. The contraction-induced increase in substance P-like immunoreactivity was reduced from a control value of 0.119 +/- 0.024 to 0.047 +/- 0.010 fmol/100 microL by DAME. Time-control experiments revealed no decrease in the release of substance P-like immunoreactivity. Thus, activation of opioid receptors modulates the transmission of group III and IV muscle afferent nerve activity through the L-7 dorsal horn.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Attenuation of the exercise pressor reflex. Effect of opioid agonist on substance P release in L-7 dorsal horn of cats. 754 80

1. Inflammatory diseases of the pancreas or diseases which cause obstruction within the biliary or within the biliary or pancreatic duct system are associated with severe pain. Although neuropeptides such as substance P are present in the biliary tree, only few capsaicin-sensitive, substance P-positive nerve fibres have been found in the ducts. In order to obtain functional evidence whether capsaicin-sensitive afferent neurones transmit nociceptive information arising from the biliopancreatic duct, blood pressure reflexes following electrical stimulation of the duct or increases in intraductal pressure were determined in barbiturate-anaesthetized rats. 2. Electrical stimulation of neurones in the biliopancreatic duct was carried out at 30 V, 3 ms, 50 Hz for 20s. In untreated animals the electrical stimulation resulted in rises in blood pressure by up to 25 mmHg, but in about a quarter of all animals tested this response was absent. Following the administration of phentolamine (7 mumol kg-1, i.p.) the blood pressure responses were changed to pronounced and reproducible depressor reflexes of -5 to -30 mmHg. Retrograde injections into the biliopancreatic duct of 300 microliters of a 154 mM sodium chloride solution produced increases in intraductal pressure of approximately 10 mmHg. This elicited shortlasting falls in blood pressure of 3-15 mmHg. Phentolamine significantly augmented the fall in blood pressure to 8-30 mmHg. 3. The depressor reflexes observed in both models after the administration of phentolamine were abolished by morphine (1 mumol kg-1, i.v.). The inhibition by morphine was reversed by naloxone (3 mumol kg-1, i.v.). Naloxone given before morphine did not affect the depressor reflex but prevented the inhibitory action of subsequently injected morphine.4. Acute s.c. injection of capsaicin (30 mg kg-1) abolished the depressor reflexes in response to both types of nociceptive stimulation in phentolamine-treated rats. The initial pressor effects of electrical stimulation were only partly inhibited by capsaicin whereas the basal depressor reflexes in response to elevation of intraductal pressure were abolished. In rats which had received capsaicin on the day before the experiment or had been treated with capsaicin as neonates, only minor rises in blood pressure were induced by electrical stimulation at the beginning of the experiment and no changes in blood pressure occurred after the administration of phentolamine. After adult or neonatal pretreatment with capsaicin the depressor reflexes in response to increased intraductal pressure were only small and were unchanged by phentolamine.5. The depressor reflexes following either electrical stimulation or increases in intraductal pressure were abolished by the unselective Beta-blocker, (-)-propranolol (3 micromol kg-1, i.p.), and greatly reduced by the Beta 1-blocker, metoprolol (6 micromol kg- 1, i.p.). The Beta2-preferring adrenoceptor antagonist, butoxamine(3 micromol kg-1, i.p.), had no effect on the depressor responses. The reflex falls in blood pressure were also abolished by hexamethonium (10 micromol kg-1, i.p.) but not by atropine (3 micromol kg-1, i.p.).6. Both models of stimulation of nociceptive afferents caused identical patterns of blood pressure responses following adrenalectomy or chemical sympathectomy. In adrenalectomized rats, the initial responses consisted of depressor reflexes which were not augmented but significantly reduced by phentolamine and further inhibited by metoprolol. In rats that had been pretreated with 6-hydroxydopamine(total dose 0.6 mmol kg-1) to accomplish chemical sympathectomy, nociceptive stimulation caused rises in blood pressure. Phentolamine treatment abolished these pressor effects but revealed only minor, if any, depressor responses that were unaffected by metoprolol.7. In summary, the hypotensive effects in both models constitute nociceptive reflexes since they are abolished by morphine and restored by naloxone. The afferent part of the reflex is mediated by nerve fibres sensitive to capsaicin. Both experimental procedures seem to elicit two, presumably separate, reflex mechanisms. Firstly, catecholamines released from the adrenal medulla elevate blood pressure or limit hypotensive responses via activation of vascular alpha receptors. Secondly, the reflex inhibition of the sympathetic nerve activity in the heart and the vasculature causes the nociceptive depressor reflexes.
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PMID:Blood pressure reflexes following activation of capsaicin-sensitive afferent neurones in the biliopancreatic duct of rats. 791 20


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