Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The analgesic activity of some opioid peptides which display a relative selectivity for either the mu-receptor subtype, [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAGO) or the delta-receptor subtype. [D-Ala2, D-Leu5]enkephalin (DADLE), [D-Ser2, Leu5]enkephalyl-Thr (DSLET) and [D-Thr2, Leu5]enkephalyl-Thr (DTLET) is highly correlated with their affinity for central or peripheral mu- but not delta-receptors. Moreover their analgesic effects as well as those elicited by degrading enzyme inhibitors (bestatin + thiorphan) of endogenous enkephalins were easily antagonized by naloxone with similar pA2 values but not by the delta-antagonist ICI 154,129. Therefore the analgesia produced by opioid peptides including endogenous enkephalins is likely connected to mu-receptor stimulation. Finally, there was no obvious potentiation by delta-agonists of the analgesia resulting from either administration of the mu-agonist morphine or endogenous enkephalins. This suggested that in the hot plate test, there is no modulation of the effect resulting from mu-receptor stimulation by a delta-receptor interaction. Likewise, enkephalinergic activity such as that due to thiorphan + bestatin does not appear to be regulated through mu- or delta-receptor stimulation.
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PMID:The mu rather than the delta subtype of opioid receptors appears to be involved in enkephalin-induced analgesia. 608 66

In order to study the preferential involvement of mu or delta receptors in the analgesic effects of enkephalins, several peptides which selectively interact with these two kinds of receptors in peripheral organs were synthesized. The inhibitory potency on the electrically stimulated mouse vas deferens (delta receptors) of the short peptide Tyr-D-Ala-Gly-NH-CH(CH3)CH2CH(CH3)2 (6) is 2100 times lower (IC50 = 1220 nM) than that of the longer and more hydrophilic peptide Tyr-D-Ser-Gly-Phe-Leu-Thr (10) (IC50 = 0.58 nM). In contrast, the IC50 values of all the synthesized compounds on the guinea pig ileum assay (mu receptors) are in the same range (100-360 nM). Likewise, their analgesic activities in mice, measured on the hot-plate test after intracerebroventricular injection, are similar. Therefore, the dissociation between antinociceptive properties in mice and potencies on the mouse vas deferens unambiguously reflects a preferential implication of mu receptors in analgesia. The possible involvement of brain delta receptors in behavioral effects is discussed.
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PMID:Evidence of the preferential involvement of mu receptors in analgesia using enkephalins highly selective for peripheral mu or delta receptors. 627 40

A comparison was made in awake rats between the analgesic and the respiratory depressant actions induced by the mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met-(O)-ol (FK-33824), and the delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu ( DADLE ) and Tyr-D-Ser-Gly-Phe-D-Leu-Thr (D-Ser2- Thr6 ), injected into the cerebral ventricles. The four opioids caused a dose-dependent analgesia (tail-flick); FK-33824 was the most potent, followed by morphine, DADLE and D-Ser2- Thr6 , and the duration of the analgesic effect of D-Ser2- Thr6 was very short. Respiratory frequency was dose-dependently depressed by FK-33824 and DADLE ; dose-response curves with morphine and D-Ser2- Thr6 could not be obtained for technical reasons. The in vivo apparent pA2 values for naloxone against the mu-agonist FK-33824 and the delta-agonist DADLE were similar in analgesia suggesting an interaction with the same type of receptor. On the other hand, in respiration studies the pA2 value for the interaction of naloxone with DADLE was significantly higher than with FK-33824. The ratio between the ED50 required to induce respiratory depression and analgesia was 1,500 times higher for FK-33824 than for DADLE . It was concluded that agonist interaction with mu-receptors can result in antinociceptive effect in the tail-flick test, whereas respiratory depression seems to require a prominent, but non-exclusive, interaction with delta-receptors.
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PMID:A comparative study in rats of the respiratory depression and analgesia induced by mu- and delta-opioid agonists. 637 10

The amino acid sequence of a newly isolated pentapeptide, neo-kyotorphin from bovine brain was synthetically verified to be Thr-Ser-Lys-Tyr-Arg corresponding to the C-terminal portion of hemoglobin alpha-chain. The synthetic neo-kyotorphin showed the dose-dependent analgesia in mice which was approximately equal to that of Leu-enkephalin.
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PMID:Neo-kyotorphin (Thr-Ser-Lys-Tyr-Arg), a new analgesic peptide. 685 39

The cold water tail-flick test in the rat is somewhat unique in that it is sensitive to the analgesic effects of delta- and kappa- in addition to mu-opioid agonists. The present study was designed to test whether a component of morphine-induced analgesia in this test might be mediated by delta- or kappa-opioid receptors. Morphine was administered icv in combination with the non-selective opioid antagonist naloxone (NLX), as well as the mu-, delta- and kappa-selective antagonists, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr (CTAP), naltrindole (NTI) and norbinaltorphimine (norBNI), respectively. Morphine induced analgesia in a dose related manner. Administration of NLX (1-10 micrograms) or CTAP (1 microgram) antagonized morphine in a competitive fashion. Neither NTI (1-10 micrograms) nor norBNI (0.1 microgram) had any effect on the morphine dose-effect curve. Thus, morphine appeared to be a selective mu agonist in the cold water tail-flick test, at least by the icv route.
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PMID:Receptor selectivity of icv morphine in the rat cold water tail-flick test. 795 48

Published results suggest that delta-opioid agonists can modulate the mu-mediated analgesia. In this work, the antinociceptive effects produced by the mu agonist [D-Ala2,NMe-Phe4,Gly-ol5]enkephalin or the mixed inhibitor of enkephalin-degrading enzymes RB 101 (N- [(R,S)-2-benzyl-3[(S)(2-amino-4-methyl- thio)butyldithio]-1-oxopropyl]-L-phenylalanine benzyl ester) were studied after administration of the systemically active and selective delta agonist Tyr-D-Ser(O-tert-butyl)-Gly-Phe-Leu- Thr(O-tert-butyl). In the hot-plate test in mice, Tyr-D-Ser(O-tert-butyl)-Gly- Phe-Leu-Thr(O-tert-butyl) (i.v.) potentiated the antinociceptive responses elicited by [D-Ala2,NMe-Phe4,Gly-ol5]enkephalin (i.v.) or RB 101 (i.v.). These facilitatory effects were reversed not only by prior administration of the delta-selective antagonist naltrindole (0.5 mg/kg s.c.), but also unexpectedly by the selective cholecystokinin CCK-A antagonist MK-329 (20 micrograms/kg i.p.). In addition, the CCK analog [Boc- Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-Phe-NH2] (a mixed CCK-A/CCK-B agonist) increased the jump latency and this effect was blocked by MK-329 (20 micrograms/kg i.p.) and by naloxone, but not by the selective CCK-B antagonist L-365,260 (5 mg/kg i.p.). In contrast, the selective CCK-B agonist BC 264 (62 micrograms/kg i.v.) produced a hyperalgesic effect that was antagonized by L-365,260 (5 mg/kg i.p.). Taken together, these findings suggest that the potentiating effects of delta agonists on mu-mediated analgesia are due to an increase in the release of endogenous CCK interacting with CCK-A and CCK-B receptors and resulting in positive and negative regulation of the endogenous opioid system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of endogenous cholecystokinin in the facilitation of mu-mediated antinociception by delta-opioid agonists. 799 17

The effect of systemically administered oxytocin and a specific oxytocin antagonist, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin, on heat pain sensitivity was examined in rats. Intraperitoneal (i.p.) oxytocin at 1 mg/kg, but not at 0.1 and 0.3 mg/kg, significantly increased response latencies on the hot-plate test. However, the rats displayed clear signs of sedation, motor impairment and vasoconstriction after 1 mg/kg oxytocin. Skin temperature on the plantar surface of the hind paws was also significantly decreased by this dose of oxytocin. The oxytocin antagonist (1 mg/kg i.p.) did not influence response latency. Since increased response latency was not the only behavioral effect of oxytocin, we conducted electrophysiological experiments to examine the effect of systemic oxytocin on the nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats. Oxytocin at 0.1 mg/kg i.p. did not influence flexor reflex magnitude, mean blood pressure or heart rate. Oxytocin at 0.3 and 1 mg/kg caused a gradual increase in blood pressure with stronger effect observed with 1 mg/kg. Neither 0.3 nor 1 mg/kg oxytocin significantly influenced the flexor reflex magnitude and heart rate. We thus conclude that systemic oxytocin did not produce analgesia in rats and the observed increase in response latency in the hot-plate test may result from the sedative and vasoconstrictive effects of this peptide. Furthermore, since the oxytocin antagonist did not significantly alter response latency on the hot-plate test, it is unlikely that endogenous oxytocin exerts a tonic effect on the pain threshold in rats.
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PMID:Is systemically administered oxytocin an analgesic in rats? 809 May 16

Intrathecal administration of morphine, Tyr-D-Ser(otbu)-Gly-Phe-Leu-Thr or dexmedetomidine for 5 to 10 days rendered rats tolerant to the test drug as measured by both behavioral and electrophysiological tests. Tolerance to the alpha-2 adrenergic agonist dexmedetomidine required a longer induction time and was not as pronounced as the tolerance to the opioid agonists, probably because lower doses of dexmedetomidine relative to the ED50 dose were used to avoid sedation. In the behavioral studies we used the tail-flick test and in the electrophysiological studies recordings were made from dorsal horn nociceptive neurons under halothane anesthesia. After completion of the behavioral testing the same animals were then used in the electrophysiological study. Cross-tolerance developed clearly between the mu opioid agonist morphine and the alpha-2 adrenergic agonist dexmedetomidine, whereas no cross-tolerance was seen between the delta opioid agonist Tyr-D-Ser(otbu)-Gly-Phe-Leu-Thr and either morphine or dexmedetomidine. This is further evidence to support the assumption that in the dorsal horn the mu opioid and the alpha-2 adrenergic receptor are linked functionally, whereas the delta opioid receptor operates independently. These results have also important clinical implications indicating the potential of delta opioid agonists to restore analgesia in a morphine-tolerant patient.
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PMID:Cross-tolerance between mu opioid and alpha-2 adrenergic receptors, but not between mu and delta opioid receptors in the spinal cord of the rat. 809 59

Antinociceptive activity of seven pentapeptide fragments of human adenovirus type 2 (Ad2) virion proteins: Thr-Val-Pro-Pro-Arg (1), Thr-Arg-Pro-Pro-Arg (2), Thr-Gly-Pro-Pro-Thr (3), Pro-Arg-Pro-Pro-Thr (4), Phe-Val-Pro-Pro-Arg (5), Ala-Arg-Pro-Pro-Ala (6), Tyr-Gly-Pro-Pro-Lys (7)--analogs of known tuftsin inhibitor Thr-Lys-Pro-Pro-Arg, was measured by hot-plate procedure. Also two tuftsin-like fragments of epitopes of HIV-1 and HIV-2: Thr-Lys-Ala-Lys (8), Thr-Lys-Glu-Lys (9), and tuftsin analog Thr-Lys-Asp-Lys (10) were tested. In the control experiments the effects of tuftsin and pentapeptide tuftsin inhibitor were also studied. The peptides 2, 4 and 5 were found to produce very strong analgesia after the icv injection. It was observed that pretreatment with peptide 8 remarkably diminished the antinociceptive effect induced by tuftsin.
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PMID:The analgesic activity of some tuftsin- and tuftsin inhibitor-like fragments of the viral coat proteins. 822 Jun 60

Based on pharmacological evidence that inhibitory amino acids mediate vaginocervical mechano-stimulation produced analgesia (VSPA), we hypothesized that inhibitory amino acids would be released endogenously in the spinal cord in response to vaginocervical mechano-stimulation (VS). This hypothesis was tested by HPLC analysis of the amino acid content of 5-min superfusates of the spinal cord before, during and after VS (400 g force applied against the cervix) in urethane-anesthetized rats. Utilizing an in vivo push-pull superfusion method, artificial cerebrospinal fluid was continuously superfused over the spinal cord through the intrathecal space surrounding the sacral-lower thoracic region. In addition, concentrations of amino acids in the superfusate were measured in response to KCl stimulation (increasing the superfusion medium from 3.4 to 40.0 mM KCl to produce non-specific depolarization), and noxious hind paw mechano-stimulation (pinching the hind paw to produce a sustained flexor response in ipsilateral hind leg). There was a significant increase in the concentration of Gly, Tau, Asp, Glu and Lys in the superfusate in response to VS (n = 8) and to KCl (n = 8), but not to hind paw stimulation (n = 5). Also, GABA concentrations increased in response to KCl, and the concentration of Ala, Ser, Gln, Thr, Arg and Phe increased in response to VS, however, GABA levels were sometimes below the limits of detection. In contrast, there was no significant change in any amino acid concentration in response to hind paw pinch stimulation, and VS did not significantly affect the concentrations of Tyr, His, Ile, Leu, Met, Trp or Val. The present findings support our hypothesis that VS releases inhibitory amino acids in the spinal cord. Moreover, other amino acids, including 'excitatory' amino acids, are released into the superfusate. The profile of amino acid release in response to VS differs from that in response to paw pinch or KCl administration.
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PMID:Release of amino acids into regional superfusates of the spinal cord by mechano-stimulation of the reproductive tract. 824 40


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