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 involvement of delta opioid receptors in supraspinal analgesia was investigated. With this aim, opioids that produced analgesia in the tail immersion test were administered i.c.v. to mice a few minutes before the irreversible antagonist, beta-funaltrexamine (beta-FNA). Protection of the respective analgesic effects from beta-FNA blockade was obtained when evaluated 24 h later. Moreover, mu ligands protected the analgesia evoked by ED50s of morphine, [D-Ala2,N-Me-Phe4,Met-(o)5-ol]enkephalin (FK 33-824), [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAGO) and human beta-endorphin at doses (ED50s) lower than those required for delta ligands (approximately ED90s) to reach a similar protection. delta Preferential ligands effectively protected the analgesia induced by ED50s of [D-Ala2,D-Leu5]enkephalin (DADLE), [D-Thr2,Leu5]enkephalin-Thr6 (DTLET) and [D-Pen2,D-Pen5]enkephalin (DPDPE) from the beta-FNA-deteriorating effect. FK 33-824 and DAGO also provided good protection of the analgesia elicited by these delta ligands whereas morphine protected much less. Binding studies after i.c.v. injection of beta-FNA showed that its alkylating effect on opioid receptors was restricted to periventricular areas. In PAG, where the mu/delta receptor ratio is about 10, [3H]DADLE specific binding was still present after ED50s of DPDPE, DAGO, morphine and DADLE as protecting agents. [3H]Dihydromorphine [( 3H]DHM) binding was well protected by ED90s of morphine and DAGO, and to a lesser extent by DPDPE and DADLE. These results suggest that delta ligands, after binding to delta receptors, also need to act upon mu receptors to produce high levels of supraspinal analgesia in the tail immersion test.
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PMID:Evaluation of delta receptor mediation of supraspinal opioid analgesia by in vivo protection against the beta-funaltrexamine antagonist effect. 256 40

Simultaneous action of morphine on supraspinal and spinal sites produces a multiplicative interaction for antinociception which may be important for the analgesia produced by systemically administered morphine. The purpose of this study was to see whether other agonists with more receptor selective opioid actions than morphine would also produce this multiplicative interaction. DAMPGO (Tyr-D-Ala2-Gly-NMePhe4-Gly-ol5), DPDPE (D-Pen2, D-Pen5, enkephalin) and U50-488H, opioid agonists highly selective for mu, delta and kappa receptors, respectively, were administered alone i.c.v. or intrathecally (i.t.) or in combination (i.c.v. plus i.t.) to determine ED50 values for the tail-flick response in mice. These ED50 values were examined isobolographically in relation to the theoretical additive ED50 values by the potency ratio method. First, DAMPGO given i.cv and i.t. was similar to morphine, indicating that simultaneous supraspinal and spinal mu agonist administration produce the multiplicative interaction. Second, concurrent administration of DPDPE or U50,488H, i.c.v. and i.t., as well as cross-over combinations of DPDPE at one and U50,488H at the other site, produced additive interactions only. The multiplicative interaction was a property characteristic of mu but not delta and kappa agonists. Based on the similarity between morphine and DAMPGO, it was postulated that both mu agonists act on redundant descending pain inhibitory pathways to produce multiplication. A second mechanism for multiplicative interaction was based on the difference between DAMPGO and morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiplicative interaction between intrathecally and intracerebroventricularly administered mu opioid agonists but limited interactions between delta and kappa agonists for antinociception in mice. 256 50

The effects of body rotation in a horizontal plane and various opiate antagonists on the nociceptive responses of a day-active microtine rodent, the meadow vole, Microtus pennsylvanicus, were examined. Intermittent rotation (70 rpm, schedule of 30 sec on, 30 sec off) for 30 min induced significant analgesic responses in the voles for 15 min after rotation. These increases in thermal response latency were blocked by intraperitoneal pretreatment with either naloxone or the irreversible mu opiate receptor antagonist beta-funaltrexamine (beta-FNA; 10 mg/kg; 24 hr pretreatment). This antagonistic effect of beta-FNA indicates mu opioid involvement in the mediation of rotation-induced analgesia. The antiopiate peptides MIF-1 (Pro-Leu-Gly-NH2) and Tyr-MIF-1 also significantly reduced, though did not completely block, body rotation-induced opiate analgesia. This suggests that Tyr-MIF-1 and MIF-1 have significant antagonistic effects on mu opioid systems that are involved in the mediation of stress (rotation)-induced analgesia.
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PMID:Differential inhibitory effects of MIF-1, Tyr-MIF-1, naloxone and beta-funaltrexamine on body rotation-induced analgesia in the meadow vole, Microtus pennsylvanicus. 257 Nov 38

The antinociceptive action (tail-flick test) of physostigmine given i.c.v. to mice was enhanced by the administration intrathecally (i.t.) of narcotic antagonists. Doses, i.t., as low as 0.1 fentog of naloxone, 0.25 ng of beta-funaltrexamine and 0.1 ng of nor-binaltorphimine enhanced physostigmine, 2 micrograms i.c.v., analgesia. These doses of opioid antagonists did not inhibit spinal mu receptors or kappa receptor agonist-induced analgesia as assessed by absence of effect on Tyr-D-Ala2-N-MePhe4-Gly-ol5 or U50,488H i.t. analgesia. Enhancing effects of the opioid antagonists were interpreted to indicate that i.c.v. physostigmine-induced analgesia was mediated spinally by an endogenous opioid which had an antagonistic effect. This putative opioid antagonist was postulated to be dynorphin A (1-17). Thus, i.t. administration of small doses of less than 10 pg of dynorphin was shown to antagonize the analgesic action of physostigmine, i.c.v. Furthermore, this effect of dynorphin was attenuated by the doses of naloxone, beta-funaltrexamine or nor-binaltorphimine which were effective in enhancing physostigmine-induced analgesia. We concluded that physostigmine given i.c.v. had two actions, the first produced analgesia and the second activated a system which had an antianalgesic effect. Evidence indicated that the latter effect was mediated by dynorphin A (1-17). This concept of dynorphin action may be the basis for some of the unusual findings of the analgesic action of naloxone in other situations and support the concept for a descending dynorphin A (1-17)-mediated antianalgesic system.
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PMID:Intracerebroventricular physostigmine-induced analgesia: enhancement by naloxone, beta-funaltrexamine and nor-binaltorphimine and antagonism by dynorphin A (1-17). 257 38

Two mammalian FMRF-NH2-like peptides have been isolated from bovine brain; an octapeptide with the structure Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F-8-F-NH2) and an octadecapeptide, Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe- NH2 (A-18-F-NH2). In the present study determinations were made of the effects of intracerebroventricular administration of IgG prepared from antisera raised against these peptides on nociception and morphine- and immobilization-induced opioid analgesia in mice. Both F-8-F-NH2-IgG and A-18-F-NH2-IgG antisera increased nociception (thermal response latency) and significantly augmented morphine- and immobilization-induced analgesia in a naloxone reversible manner, with F-8-F-NH2-IgG antisera having a greater effect than A-18-F-NH2-IgG antisera. These results provide further evidence that mammalian FMRF-NH2-like peptides function as endogenous opiate antagonists and have a role in the mediation of antinociception.
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PMID:IgG from antiserum against endogenous mammalian FMRF-NH2-related peptides augments morphine- and stress-induced analgesia in mice. 258 16

Dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), a naturally occurring peptide isolated from arboreal frog skin, is endowed with outstanding structural and biological features. It has no structural community with the sequence of mammalian opioid peptides and is a unique example of a D-aminoacid containing peptide which is synthesized via ribosomal route. Dermorphin is the most potent of the opioid peptides or opiates in producing long lasting analgesia and catalepsy. Since most amphibians' secretory peptides have counterparts in the mammalian central nervous system and gastrointestinal tract, we have developed a sensitive enzyme immunoassay that can detect 1 pg dermorphin to verify the possibility of dermorphin or dermorphin-related peptides occurrence in mammalian tissues. Dermorphin-related peptides were purified by fast protein liquid chromatography followed by reverse phase high pressure liquid chromatography. Identification was achieved by chromatographic comparison with synthetic standards and immunological analysis. A peptide behaving like authentic dermorphin was detected (2 ng/g) in rat small intestine. Immunoreactive species of higher Mr were also detected in the brain, adrenal glands and gastrointestinal tract, they may represent extended forms of dermorphin or homologous peptides.
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PMID:Dermorphin and related peptides in rat tissues. 264 50

I.c.v. injection of 1 nmol N-ethylmaleimide (NEM) into mice interfered with opioid-induced supraspinal analgesia, as assessed in the warm water tail-flick test. This effect of NEM was long-lasting (more than 3 days), non-competitive and differentially inhibited by the opioids studied. The analgesia induced by [D-Ala2,D-Leu5]enkephalin (DADLE), [D-Ala2,Met5]enkephalinamide (DAME) and [D-Pen2,D-Pen5]enkephalin (DPDPE) was greatly reduced in NEM-treated mice. The antinociception elicited by [D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAGO) was also impaired although to a lesser extent. In contrast, the activity of morphine and etorphine remained unchanged. NEM-sensitive opioids coadministered with morphine antagonized the analgesia elicited by the alkaloid in NEM-treated mice. The administration of naltrexone or DADLE, DAGO, [D-Ala2,N-MePhe4,Met-(O)5-ol]enkephalin (FK-33824) and morphine in doses equivalent to the ED90 doses for inducing analgesia, a few minutes before NEM prevented it from interfering with DADLE-elicited supraspinal analgesia when evaluated 24 h later. In contrast, the selective delta antagonist, ICI 174864, did not protect the DADLE-induced analgesia against the effect of NEM. We suggest that NEM produced its effect by acting upon a site that appears to be distal to the receptor binding site, presumably located on the guanine nucleotide binding regulatory proteins, Gi/Go. Therefore, these transducer proteins might play a key role in the effects displayed by opioids when acting via the mu receptor-Gi/Go complexes.
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PMID:Intracerebroventricular N-ethylmaleimide differentially reduces supraspinal opioid analgesia in mice. 267 63

Two peptides that are structurally related to the molluscan tetrapeptide Phe-Met-Arg-Phe-NH2 (FMRF-NH2) were recently isolated from bovine brain extract (Yang et al.: Proc. Natl. Acad. Sci. USA 82:7757-7761, '85). These peptides have an attenuating effect on morphine-induced analgesia when injected intracerebroventricularly in rats. Antisera against the two peptides--an octapeptide, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F8F-NH2), and an octadecapeptide, Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe- NH2 (A18F-NH2)--were raised in rabbits and characterized with standard radioimmunoassay and immunohistochemical blocking controls. This study was aimed at localizing neurons in the rat brain that contain immunoreactivity for these peptides. Cryostat sections of normal and colchicine-treated Sprague-Dawley rat brains were incubated with the specific antisera and the immunoreactivity was visualized by the PAP or the FITC method. Immunoreactive neurons were detected in the hypothalamus and nucleus of the solitary tract. Relatively dense networks of fibers and terminals were observed in the lateral parabrachial nucleus and in the nucleus of the solitary tract. Fibers and terminals were also seen in the lateral septum, amygdala, hypothalamus, neurohypophysis, thalamus, periaqueductal gray, and several medullary nuclei. In these areas the immunoreactivity was abolished when the antisera were incubated with the corresponding synthetic peptides F8F-NH2 and A18F-NH2. Preincubation of the antisera with neuropeptide Y (NPY) did not affect the staining. The results suggest that there are neurons in the rat brain that contain F8F-NH2- and A18F-NH2-like peptides. The neuronal system described here may have a role in the regulation of autonomic functions, such as hypothalamic control and respiratory functions. The neuronal connections of the cells containing F8F-NH2- and A18F-NH2-like peptides remain to be studied.
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PMID:Immunohistochemical distribution and partial characterization of FLFQPQRFamidelike peptides in the central nervous system of rats. 279 21

The tail-flick assay in chronic implanted rats was used to test the analgesic potency of agonists selective for mu opioid receptors: [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), Tyr-D-Ala-Gly-NH(CH2)2-CH(CH3)2 (TRIMU 5) and for delta receptor subtypes: [D-Ser2,Leu5]enkephalyl-Thr6 (DSLET), [D-Thr2,Leu5]enkephalyl-Thr6 (DTLET) and cyclic [D-Pen2,L-Pen5]enkephalin (DPLPE). DAGO produced an analgesic response at a concentration 500 times lower than DPLPE. The relative activity of these compounds was significantly correlated with their affinity for central or peripheral mu receptors but not with their delta receptor affinity. Diffusion studies of tritiated mu and delta agonists showed that after i.c.v. injection, these enkephalin analogues remained essentially localized within supraspinal structures. Taken together these results suggest strongly that the analgesia produced at the supraspinal level by opioid peptides is related to mu receptor stimulation.
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PMID:Use of mu and delta opioid peptides of various selectivity gives further evidence of specific involvement of mu opioid receptors in supraspinal analgesia (tail-flick test). 282 13

The purpose of these investigations was to determine 1) whether peripherally located mu, delta and kappa opioid receptors can inhibit the rate of gastrointestinal transit and, if so, 2) do peripheral opioid receptors mediate the constipation caused by systemic morphine? and 3) whether constipation can be separated from analgesia on the basis of different sites of action. We studied the effects of peripherally administered (s.c.) mu, delta and kappa opioid receptor selective agonists on the rate of gastrointestinal transit in mice. We used peptidergic agonists with high peripheral selectivity (limited ability to cross the blood-brain barrier) including [MePhe3,D-Pro4]morphiceptin (PL017) (mu), [D-Pen2,D-Pen5]enkephalin (DPDPE) (delta) and Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg (dynorphin 1-9) (kappa). As peripheral selectivity is dose-related, we included the hot-plate test as an index of that dose at which each compound lost its peripheral selectivity and entered the central nervous system. When given s.c., [MePhe3,D-Pro4]morphiceptin inhibited transit (IC50 = 0.37 mg/kg s.c.) at doses much lower than those needed to produce analgesia (A50 = 30 mg/kg s.c.), indicating that peripheral mu receptors can inhibit transit independently of central mu receptors. The independence of peripheral mu antitransit receptors from central receptors was demonstrated further as the lack of antagonism of s.c. [MePhe3,D-Pro4]morphiceptin antitransit effects by simultaneous i.c.v. administration of the mu receptor antagonist D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP) (1 microgram i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peptide opioid antagonist separates peripheral and central opioid antitransit effects. 282 48


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