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)

Effects of noxious cutaneous stimulation on the tail flick reflex were examined in the anaesthetized rat. Noxious stimulation was applied by immersing the distal 4 cm of the tail in water at 55 degrees C for 1.5 min. The tail flick reflex was tested at 3 min intervals by applying a noxious radiant heat stimulus to a region of the tail 10 cm proximal to the tip. Tail immersion reduced reaction time to tail flick by 30% and 20% at 0.5 and 3.5 min after immersion, respectively. Reaction time returned to control at 6.5 min and tended to increase above baseline values at 9.5 and 12.5 min. Naloxone (10 mg/kg, i.p.) potentiated the effects of tail immersion on reaction time and prevented the increase above baseline. When the surface temperature of the skin used to evoke the tail flick reflex was raised by 10 degrees C using innocuous radiant heat, reaction time was not significantly different from the control, suggesting that an increase in skin temperature per se is insufficient to account for the response to immersion. Intrathecal administration of a substance P antagonist (1 nmol) attenuated the response to tail immersion. These results indicate that noxious cutaneous stimulation may release an agent in the spinal cord which facilitates the tail flick reflex, and that this agent is antagonized by a substance P antagonist.
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PMID:Facilitation of the tail-flick reflex by noxious cutaneous stimulation in the rat: antagonism by a substance P analogue. 246 Jan 94

Using an electromyographic technique, an ascending excitatory response was recorded "in vitro" in the presence of atropine in the cat small intestine up to 70 mm orally with respect to the site of repetitive transmural nerve stimulation. This non-cholinergic ascending excitatory response was characterized by an increase in the slow wave amplitude and spiking activity. This response was reversibly abolished by Tetrodotoxin (3,1 X 10(-6) M) but remained unchanged after exposure of the intestine to: Hexamethonium (4,9 X 10(-6) M) plus Tubocurarine (1,4 X 10(-5) M), Guanethidine (5 X 10(-7) to 5 X 10(-5) M), Domperidone (2,3 X 10(-7) to 2,3 X 10(-5) M), Naloxone (3 X 10(-7) to 3 X 10(-5) M), Methysergide (2,8 X 10(-7) to 2,8 X 10(-5) M), Metergoline (2,4 X 10(-5) M), Methiotepin (2,1 X 10(-5) M) and Mepyramine (2,3 X 10(-5) M). This response was unaffected by the substance P analogues, D-Pro2, D-Phe7, D-Trp9-Substance P (10(-5) M) or D-Pro2, D-Trp7-9-Substance P (10(-5) M) but was reversibly abolished after exposure of the intestine to substance P (10(-6) M). Moreover substance P still effectively abolished this response in the presence of any two of the above analogues. The results of the present study show that the non-cholinergic excitatory response elicited in the cat small intestine due to the activity of long ascending pathways probably involved substance P. The functional significance of this response is discussed.
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PMID:Non-cholinergic ascending excitatory response in the cat small intestine: possible involvement of substance P. 246 25

An in vitro model system for analysis of presynaptic inhibitory actions of spinal opioids has been applied. Embryonic sensory neurons derived from chick dorsal root ganglia were grown in primary cell culture, and the release of substance P was evoked by electrical field stimulation during exposure to drugs with well-demonstrated affinity for opioid receptors. This allowed a pharmacologic characterization of the inhibitory actions of specific opioid agonists on the release of substance P as measured by radioimmunoassay (RIA). Sufentanil (0.5 microM), a high affinity mu receptor agonist, U-50,488H (25 microM), a selective kappa receptor agonist, and morphine (10 microM), an agonist with high affinity for mu and delta receptors, inhibited the evoked release of substance P by approximately 60%, 40%, and 50%, respectively. For sufentanil the response was demonstrated to be dose-dependent. As is the case for its analgesic action in vivo, morphine was approximately 50-fold less potent than sufentanil on a molar basis in this assay. The actions of sufentanil, U-50-488H and morphine were mimicked by the endogenous opioid peptide met-enkephalin, and its stable synthetic analog D-ala2-met5-enkephalinamide (DAME). Naloxone (25 microM), an opioid receptor antagonist, blocked the inhibitory action of sufentanil (0.5 microM), morphine (5 microM), and DAME (5 microM), but not U-50,488H (10 microM). The action of U-50,488H was partially blocked by the antagonist naltrexone (25 microM). Stereo-selectivity of agonist action was confirmed by the failure of dextrorphan (50 microM), an inactive opioid isomer, to inhibit the release of substance P.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sufentanil, morphine, met-enkephalin, and kappa-agonist (U-50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions. 246 89

This study describes the first direct demonstration that naloxone evokes the release of both substance P-like immunoreactivity (SPLI) and [Leu]enkephalin-like immunoreactivity (LELI) form opiate tolerant/dependent guinea pig ileum longitudinal muscle myenteric plexus (LMMP). The basal release of SPLI was 0.5 pg/mg of tissue per 2 min and LELI was 60 fg/mg of tissue per 2 min. Naloxone at 1 microM concentration evoked both SPLI and LELI release from in vitro as well as rapid in vivo opiate tolerant/dependent LMMP. The magnitudes were nearly double the basal release. In opiate-naive LMMP, naloxone also evoked a significant LELI release suggesting that the enkephalinergic neurons in the LMMP are under a tonic endogenous opioid inhibitory control.
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PMID:Substance P and [leucine]enkephalin release in guinea pig ileum during naloxone-precipitated morphine withdrawal. 246 64

Rat peritoneal mast cells were exposed to the neurohormone and basic opioid peptide beta-endorphin. beta-Endorphin induced a dose-dependent release of histamine from the mast cells. A significant histamine release was found at 5 mumol/l of beta-endorphin and maximal release (35% of total) at 20 mumol/l. The histamine release process was very rapid and terminated within 30 s at 37 C, and in this sense is very similar to the histamine release induced by compound 48/80 or neurotensin. The histamine release was temperature-dependent showing an optimum release around 30 C, and it was independent of available extracellular calcium, but was inhibited in the presence of high extracellular calcium concentrations. Naloxone, only in very high concentrations (10 mmol/l), inhibited the release, and the very same concentration also inhibited the neurotensin - as well as the compound 48/80-induced histamine release. Cromoglycate and benzalkoniumchloride, a 48/80 antagonist, both produced a progressive dose-dependent inhibition of beta-endorphin-, neurotensin- as well as compound 48/80-induced histamine release. Taken together, the findings indicate that the opioid peptide beta-endorphin induces a selective, energy-dependent release of histamine from peritoneal rat mast cells. The pattern of release has much in common with that of compound 48/80 and other basic peptides, such as neurotensin and substance P. In addition this pattern of release is similar to that induced by dynorphin.
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PMID:Characteristics of beta-endorphin-induced histamine release from rat serosal mast cells. Comparison with neurotensin, dynorphin and compound 48/80. 246 22

Previous investigations find that morphine administered i.c.v. induces antinociception directly at supraspinal sites and indirectly via activation of descending spinal systems. Independent experimentation suggests substance P and N-methyl-D-aspartate (NMDA) administered intrathecally (i.t.) can act as putative pain neurotransmitters to stimulate afferent pathways mediating nociception. The present studies were designed to determine whether a functional link exists between these observations. Mice were administered morphine i.c.v. 15 min before i.t. injections of substance P or NMDA. Additional investigations utilized coadministration of substance P or NMDA i.t. with one of several antagonists. Morphine administered i.c.v. inhibited both substance P- and NMDA-induced behavior in a dose-dependent manner. Coadministration of noradrenergic or adenosine receptor antagonists with substance P or NMDA i.t. dose-dependently reversed morphine (i.c.v.)-mediated inhibition. Methysergide injected i.t. caused significant, but only partially effective, antagonism of the effects of morphine (i.c.v.). Naloxone coadministered i.t. was effective in reversing morphine (i.c.v.)-mediated inhibition of NMDA-induced behavior, but ineffective in the substance P assay. These data demonstrate a functional link between activation of descending systems mediating antinociception by morphine (i.c.v.) and inhibition of putative pain neurotransmitters by spinally active antinociceptive agents. The potential involvement of serotonergic and opioid spinal systems is not clear, but noradrenergic and adenosine spinal pathways appear to play an important role in the indirect actions of morphine (i.c.v.). Differences in the inhibition of NMDA- and substance P-induced behavior also provide evidence for the presence of substance P and NMDA receptors in separate afferent pathways transmitting nociceptive stimuli.
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PMID:Morphine (intracerebroventricular) activates spinal systems to inhibit behavior induced by putative pain neurotransmitters. 248 Oct 30

Intrathecal (IT) injection of KK-3, a leucine-enkephalin analogue with weak, naloxone-reversible analgesic effect, produced behavior consisting of scratching, biting, licking and characteristic convulsion-like symptoms in mice. Naloxone or Mr2266 did not affect the behavior, suggesting a difference in the mechanisms for the production of the behavior and the analgesic effect. The behavior, except the convulsive symptom and the lag time of a couple of min for onset of the behavior, are quite similar to that elicited by IT substance P (SP). D-Pro2-D-Trp7,9-substance P, a SP antagonist, completely suppressed all the behavior induced by KK-3, indicating that the behavior is attributable to SP. By radioimmunoassay, it was found that SP was released by stimulation with KK-3 from the isolated spinal cord preparation of newborn rat. Intrathecal pretreatment with capsaicin, a depleter of SP, suppressed the KK-3-induced behavior, but did not affect the SP-evoked behavior. These results suggest that KK-3 acts as a releaser of SP in the spinal dorsal horn, and consequently produces SP-like behavior. Thus, a novel pharmacological action, the release of substance P from spinal cord by the IT injection of endogenous opioid peptide analogue, was demonstrated.
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PMID:Release of substance P by intrathecal KK-3, a newly synthesized Leu-enkephalin derivative. 248 10

Capsaicin has been shown to evoke the release of substance P (SP) from small diameter primary afferent fibers. Using an in vivo perfusion of the rat spinal cord, this study examined the pharmacology of opioid receptor systems which modulate the capsaicin-evoked release of SP. The addition of capsaicin (200 microM) to the perfusate raised SP-like immunoreactivity (SP-LI) from resting levels of 31 +/- 5 to 74 +/- 14 pg/ml or an increase of 139% above the baseline. Using high pressure liquid chromatography (HPLC) the identity of the released SP-LI was determined to coelute primarily with authentic SP or the oxidized form of SP. Opioid receptor agonists were added to the perfusate and their ability to inhibit capsaicin-evoked release of SP-LI was assessed. Morphine (10-100 microM), DAGO (1-100 microM), DPLPE (10-100 microM), but not U50488H (100 microM) produced a dose-dependent reduction in the capsaicin-evoked release of SP-LI. Pretreatment with the opioid receptor antagonist naloxone (1 mg/kg, IP) had no effect on the basal or capsaicin-evoked release of SP-LI. Naloxone pretreatment was able to antagonize completely the opioid-produced inhibition of capsaicin-evoked SP-LI release. These data indicate that the release of SP from primary afferent fibers can be modulated by the activation of mu or delta but not kappa opioid receptors. Further, these data support the hypothesis that spinally administered mu and delta opioid agonists may produce their antinociceptive effect through the presynaptic inhibition of neuropeptide release from small diameter primary afferent fibers.
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PMID:Opioid modulation of capsaicin-evoked release of substance P from rat spinal cord in vivo. 248 63

The participation of opioid neurons in the regulation of peristalsis was examined in a rat colonic segment that permits separate characterization of the components of the peristaltic reflex (ascending contraction and descending relaxation). Naloxone increased descending relaxation and decreased ascending contraction; opioid peptides [methionine-enkephalin (Met-Enk), dynorphin-13, and morphiceptin] had opposite effects. Naloxone increased, and Met-Enk decreased, vasoactive intestinal peptide (VIP) release during each component of the reflex. The changes in VIP release reinforced the direct effects of naloxone and opioid peptides on circular muscle tone, providing an explanation for the effects of these agents on the two components of the peristaltic reflex. Dynorphin release decreased during descending relaxation and increased during ascending contraction, reflecting corresponding changes in opioid neural activity. Based on these results a model is proposed, according to which a decrease in opioid neural activity during the initial phase (i.e., descending relaxation) results in direct and VIP-mediated decrease in circular muscle tone. Restoration of opioid neural activity during the subsequent phase (i.e., ascending contraction) increases circular muscle tone and reinforces the action of tachykinin and cholinergic motor neurons, which are the direct mediators of ascending contraction.
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PMID:Role of opioid neurons in the regulation of intestinal peristalsis. 288 19

In rats, bilateral injection of muscimol (30-60 ng/site) into the medial substantia nigra zona reticulata exerted an antinociceptive effect in the hotplate and tail-flick tests. Injections of muscimol into the substantia nigra also induced intense stereotyped behavior and self-injurious behavior (SIB). Tail-flick and hindpaw-lick responses were inhibited between 30 and 120 min after muscimol, but recovered by 240 min. The antinociceptive responses were not due to motor impairment or ataxia induced by muscimol because a variety of highly-coordinated stereotyped behavioral responses, including rearing, sniffing, head bobbing and licking occurred concurrently. Injection of muscimol into the deep mesencephalic nucleus (DpMcN) also inhibited the tail-flick and hindpaw-lick responses and caused stereotyped behavior but did not induce self-injurious behavior. Injections of muscimol into the substantia nigra, angled (45 degrees) to avoid passing through the deep mesencephalic nucleus, still exerted antinociceptive activity and caused self-injurious behavior. Bilateral microinjections of baclofen (300 ng), 4,5,6,7-tetrahydroisoxazols (5,40c)pyridin-3-ol (THIP; 300 ng), sodium valproate + D,L-diaminobutyric acid (1 microgram), substance P (2.5 micrograms) or D-Pro2-D-Trp7.9-substance P (2.5 micrograms), all suppressed hindpaw-lick responses, although only THIP reduced tail-flick responses. None of these treatments evoked self-injurious behavior. Naloxone (10 mg/kg), picrotoxin (5 mg/kg) or atropine (10 mg/kg) injection of muscimol into the substantia nigra (60 ng) or a single pretreatment with p-chlorophenylalanine diethyl ester (PCPA; 500 mg/kg; 48 hr prior to muscimol) failed to suppress the hindpaw-lick response or self-injurious behavior. These results suggest that the injection of muscimol into the substantia nigra evokes a centrally-mediated antinociception which alone is not sufficient to induce self-injurious behavior. Both antinociception and self-injurious behavior after injection of muscimol into the substantia nigra appear unrelated to cholinergic, serotoninergic, or naloxone-sensitive nociceptive systems; however, the role of activation of gamma-aminobutyric acid (GABA) receptors in these actions of muscimol also remains to be clarified.
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PMID:Evaluation of the role of antinociception in self-injurious behavior following intranigral injection of muscimol. 294 27


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