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

Possible involvement of cerebral delta opioid receptors in antinociceptive processes was studied in a test utilizing heat as the noxious thermal stimulus. The investigation focused on selective agonists and antagonists for mu and delta opioid receptors. Morphine and [D-Ala2,NMPhe4, Gly-ol]enkephalin (DAGO) were used as agonists for the mu receptor while [D-Pen2,D-Pen5]enkephalin (DPDPE) was the agonist for the delta receptor. Two approaches were employed: first, the intracerebroventricular (i.c.v.) analgesic activity of the agonists was determined in the absence, and in the presence of graded i.c.v. doses of the selective delta antagonist, ICI 174,864 (N,N diallyl-Tyr-Aib-Aib-Phe-Leu-OH) (where Aib is alpha-aminoisobutyric acid); second, acute tolerance to morphine was produced and the possible presence of acute cross-tolerance between subcutaneous (s.c.) morphine and the delta agonist investigated. ICI 174,864 antagonized the analgesia produced by DPDPE, but not that resulting from morphine or DAGO. Morphine pretreatment resulted in the development of acute tolerance to i.c.v. morphine, and acute cross-tolerance to i.c.v. DAGO, but not to i.c.v. DPDPE. These results provide evidence that both cerebral delta and mu opioid receptors are responsible for the mediation of analgesia in tests utilizing heat as the nociceptive stimulus.
 ...
PMID:Evidence for delta receptor mediation of [D-Pen2,D-Pen5]-enkephalin (DPDPE) analgesia in mice. 282 89

The role of mu and delta opioid receptors in the spinal and supraspinal analgesic actions of morphine and [D-Pen2, L-Pen5] enkephalin were examined in the tail-flick test utilizing the mu opioid receptor deficient CXBK mouse and BALB/cBy and C57BL/6By, the progenitor strains of CXBK. The analgesic effects of i.c.v. administered morphine were equivalent in the CRS-CD1 (Swiss) standard laboratory mice and the progenitor strains of CXBK. Morphine did not, however, produce analgesia in the CXBK mice at doses greater than 10 times the ED50 dose in the progenitor strains. Similarly, the analgesic effect of i.c.v. [D-Ala2, NMePhe4, Gly-ol]enkephalin, a highly selective mu receptor peptide agonist, also was reduced greatly in the CXBK mice. These data are consistent with the deficiency in mu opioid receptors observed autoradiographically in this strain. In contrast, the highly selective delta opioid receptor peptide agonist [D-Pen2, L-Pen5]enkephalin was equipotent i.c.v. in the CXBK mice and in the progenitor strains of CXBK. In contrast to the effects produced by i.c.v. administration, the analgesic effects of intrathecally administered morphine were similar between CRS-CD1 and CXBX strains of mice. These results suggest that 1) both mu and delta opioid receptors can mediate supraspinal analgesia and 2) that the receptor(s) involved in spinally mediated analgesia is (are) quite distinct from those involved supraspinally.
 ...
PMID:Examination of the involvement of supraspinal and spinal mu and delta opioid receptors in analgesia using the mu receptor deficient CXBK mouse. 283 33

Earlier studies from this laboratory had indicated that there is a selective increase in the density of brain kappa opioid receptors labeled with [3H]ethylketocyclazocine in spontaneously hypertensive (SHR) rats in comparison to normotensive Wistar-Kyoto rats. The binding of a mu-ligand, [3H]naltrexone, and a delta-ligand, [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr, to brain membranes of hypertensive and normotensive rats did not differ. The present studies were undertaken to determine further the role of kappa opioid receptors in hypertension. The binding of [3H]ethylketocyclazocine to brain membranes of hypertensive rats was much greater than those of normotensive rats. The density of kappa receptors was significantly higher in hypothalamic membranes of hypertensive rats as compared to normotensive rats. In order to determine the functional significance of the increased density of brain kappa opioid receptors in SHR rats, the effect of the kappa receptor agonists, tifluadom, U-50,488H and bremazocine, on two known actions associated with kappa receptors, namely analgesia and diuresis, were determined in SHR and normotensive rats. All three kappa agonists produced dose-dependent analgesia as measured by the tail-flick test. The intensity of the analgesic responses at each dose of the drugs in SHR rats was much greater than in normotensive Wistar-Kyoto rats. The kappa drugs also produced dose-dependent diuretic effects when the rats were loaded with 5% saline intragastrically. The increases in the volumes of urine produced by kappa drugs were much greater in SHR rats in comparison to normotensive rats. The basal tail-flick reaction time or urinary output in the two strains did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Kappa opioid receptor activity in spontaneously hypertensive rats. 283 73

Previously, we reported on an opioid antagonist, nor-binaltorphimine (nor-BNI), that had high selectivity for kappa opioid receptors in smooth muscle preparations. In this study, nor-BNI administered either s.c. or i.c.v. was shown to antagonize significantly the antinociceptive effects of the kappa opioid agonists, ethylketazocine and U-50,488H at doses that had no effect on the antinociceptive effect of mu agonists, morphine and [D-Ala3, MePhe4, Gly-ol5]enkephalin and the delta agonist, [D-Pen3, D-Pen5]enkephalin. Nor-BNI and U-50,488H were used to demonstrate that kappa opioid receptors in the spinal cord were more important than those located supraspinally for kappa-mediated analgesia. Nor-BNI also possessed high affinity and high selectivity for kappa opioid receptors in the receptor binding assay. However, the comparatively low selectivity of BNI in receptor binding studies did not correlate with the high pharmacologic selectivity for kappa receptors.
 ...
PMID:Nor-binaltorphimine, a highly selective kappa-opioid antagonist in analgesic and receptor binding assays. 283 64

1. Meptazinol is an interesting opioid-producing naloxone-reversible analgesia with few cardiovascular and respiratory effects. Recent studies indicate that mu 1 opioid receptors mediate meptazinol analgesia. Using a computerized autoradiographic subtraction technique, we have examined the regional distribution of meptazinol-sensitive [3H][D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO) binding and compared this with the distribution of mu 1 binding determined by competition with low [D-Ala2,D-Leu5]enkephalin (DADL) concentrations. 2. Meptazinol and DADL lowered [3H]DAGO to similar extents in most brain regions studied. The greatest levels of inhibition were observed in the periaqueductal gray, interpeduncular nucleus, thalamus, hypothalamus, and hippocampus. Low levels of inhibition were found in the temporal and frontal cortex. The correlation between the inhibition of [3H]DAGO binding by meptazinol and that by DADL was high (r = 0.83), consistent with the binding of meptazinol to mu 1 sites.
 ...
PMID:Quantitative autoradiographic distribution of meptazinol-sensitive binding sites in rat brain. 285 61

Forced swimming in warm or cold water can lead to immobility and analgesia in mice. In this report we demonstrate that the peptide MIF-1 (Pro-Leu-Gly-NH2) was able to attenuate the analgesia induced by swimming in warm water, but not that induced by swimming in cold water. In addition, we show that the analgesia and the immobility may be differentially mediated since MIF-1 was able to reduce the immobility at doses different from those necessary to reduce the analgesia. These results confirm previous research indicating that MIF-1 may act as an anti-opiate and further demonstrate that MIF-1 affects analgesia induced by stress.
 ...
PMID:MIF-1 antagonizes warm-, but not cold-water stress-induced analgesia: dissociation from immobility. 287 47

The effects of i.c.v. administration of the peptide FMRFamide (Phe-Met-Arg-Phe-NH2), as well as i.p. injections of PLG (Pro-Leu-Gly-NH2) and the opiate antagonist, naloxone, on immobilization-induced analgesia and locomotor activity were examined in CF-1 and C57BL strains of mice. Both naloxone (1.0 mg/kg) and FMRFamide (0.10-1.0 microgram) blocked the experimentally induced analgesia and activity, whereas PLG (0.10-10 mg/kg) suppressed only analgesia. These results indicate that FMRFamide (or FMRFamide-like neuropeptides) and PLG may function as differential antagonists of the behavioral and physiological consequences of endogenous opioid activation.
 ...
PMID:Inhibitory influences of FMRFamide and PLG on stress-induced opioid analgesia and activity. 287 3

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), a biologically active brain peptide, has previously been shown to antagonize the analgesia induced by morphine. In this report experiments are described in which mice were tested on the hot-plate in three models of antinociception - shock, novel environment, and warm-water swim - after the administration of various doses of Tyr-MIF-1 without any exogenous opiates. The peptide reduced the antinociception produced by all three methods of inducing endogenous antinociception. These results add further support for the existence of peptides like Tyr-MIF-1 that act as opiate antagonists.
 ...
PMID:Tyr-MIF-1 attenuates antinociceptive responses induced by three models of stress-analgesia. 288 5

Male rats were injected s.c. once daily during the first week of life with beta-endorphin (BE), morphiceptin, the antiopiate Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), or one of the two opiate peptides in combination Tyr-MIF-1. Pups treated with neonatal BE removed their tails from a series of increasingly hot water baths significantly faster than controls on day 9, confirming our earlier studies. In addition, we found that Tyr-MIF-1 blocked this effect of BE. At 4.5 months, latency to lick a hindpaw in the hot-plate test was significantly faster in groups given BE alone, morphiceptin alone, or the control vehicle than in any of the 3 groups given Tyr-MIF-1. At 6 months the two groups given opiate peptides alone showed faster tail-flick latencies than the controls and the groups given Tyr-MIF-1. These results indicated that the long-term nociceptive changes induced by the opiate peptides were opposite to those induced by Tyr-MIF-1. Mean tail-flick latencies of the groups on day 9 correlated well with hot-plate and tail-flick scores in adulthood, indicating that the effects of the peptides were persistent. The neonatal peptide treatments did not differentially affect the analgesia induced by the stress of footshock or warm-water swim. Rats given either of the opiate peptides alone tended to fall off a rotorod faster than those in the other groups. These results support the role of Tyr-MIF-1 as an antiopiate and further illustrate the long-term effects of neonatally administered peptides.
 ...
PMID:Long-term hyperalgesia induced by neonatal beta-endorphin and morphiceptin is blocked by neonatal Tyr-MIF-1. 288 15

A new series of 12 dermorphin tetrapeptides, W-Tyr-D-MetO-Phe-Xaa-Y (W = H, H2NC = (NH); Xaa = Gly, Sar, D-Ala; Y = OH, OCH3, NH2) were prepared by traditional methods in solution and tested for opioid activity. In binding studies based on displacement of mu, delta, and kappa opioid receptor selective radiolabels from guinea pig brain membranes, the new analogues showed a negligible affinity for the kappa binding site and a preference for mu- over delta-receptors with an evident dependence on N- and/or C-terminal modifications; H-Tyr-D-MetO-Phe-Gly-OCH3 was shown to be one of the most selective mu-receptor ligands reported to date. All these tetrapeptides display dose-related naloxone-reversible antinociceptive effects following intracerebroventricular (icv) or subcutaneous (sc) administrations in mice. In comparison to morphine, H-Tyr-D-MetO-Phe-Sar-NH2 and the guanidino derivative H2NC = (NH)-Tyr-D-MetO-Phe-Gly-NH2 showed lower affinity for mu, delta, and kappa sites but exceptionally stronger analgesia: respectively they are 560 and 1550 times as potent an analgesic as morphine. Among analogues tested after sc administration, H-Tyr-D-MetO-Phe-Sar-NH2 and H-Tyr-D-MetO-Phe-D-Ala-OH displayed the highest activities; they were respectively 22 and 30 times more potent than morphine on a molar basis. These results indicate that N- or C-terminal modifications and substitution at position 2 or 4 of dermorphin-(1-4) peptide do not only influence the affinity of the resulting analogues to opioid receptors but also may favorably alter their pharmacokinetic properties.
 ...
PMID:Synthesis and activity profiles of new dermorphin-(1-4) peptide analogues. 288 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>