Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bremazocine, a benzomorphan, has been reported to have kappa, mu and epsilon opioid receptor binding activities. The present studies were then designed to determine what types of opioid receptors and neurotransmitters were involved in inhibiting the tail-flick response induced by bremazocine in male ICR mice. U50, 488H, a prototypic kappa agonist, was used for comparison. Bremazocine, at doses from 0.1 to 1 microgram given i.c.v., dose-dependently inhibited the tail-flick response. The paw-licking hot plate response, even at high doses of bremazocine, was not completely inhibited. The inhibition of the tail-flick response induced by bremazocine (1 microgram) given i.c.v. was blocked by i.c.v. coadministration of beta-endorphin-(1-27) (3 and 6 micrograms), an epsilon opioid receptor antagonist and norbinaltorphimine (4 micrograms), a kappa opioid receptor antagonist. On the other hand, the inhibition induced by i.c.v. U50,488H (40 micrograms) was blocked by i.c.v. norbinaltorphimine, but not beta-endorphin-(1-27). D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2 (CTOP; 0.5 microgram) and beta-funaltrexamine (beta-FNA; 2.5 micrograms), selective mu opioid receptor antagonists, and ICI 174,864 (10 micrograms), a delta-opioid receptor antagonist, which blocked the effects induced by DAMGO (16 ng) and DPDPE (20 micrograms), respectively, did not block inhibition of the tail-flick response induced by bremazocine (1 microgram) given i.c.v. The inhibition of the tail-flick response induced by i.t. administration of bremazocine (1 microgram) was blocked by i.t. coadministration of norbinaltorphimine but not CTOP, ICI 174,864, or beta-endorphin-(1-27).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Involvement of epsilon and kappa opioid receptors in inhibition of the tail-flick response induced by bremazocine in the mouse. 165 27

The periaqueductal gray is a brain region of considerable interest. It is innervated by monoamine-containing neurons as well as by a variety of peptidergic fiber systems, and it participates in the regulation of various functions. Virtually nothing is known about monoamine release in the periaqueductal gray and its receptor-mediated modulation. We therefore studied the release of radioactivity from periaqueductal gray slices preloaded with tritriated monoamines, using an in vitro superfusion method. The release of radioactivity from superfused periaqueductal gray slices after preloading of the tissue with [3H]noradrenaline increased upon electrical stimulation in a frequency-dependent manner. The stimulus-evoked release of radioactivity was Ca(2+)-dependent. Clonidine reduced and yohimbine enhanced the release. The inhibition curve for the effect of clonidine was shifted to the right in the presence of 10(-6) M yohimbine. While phenylephrine, isoprenaline, SK & F 38393, quinpirole, carbachol, [Arg8]vasopressin, alpha-MSH and ACTH-(1-24), at a concentration of 10(-6) M, did not influence the electrically evoked release of radioactivity, [Leu5]enkephalin reduced it. The selective mu-opioid receptor agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin and [D-Arg2,Lys4]-demorphin-(1----4)-amide reduced the release of radioactivity, whereas the selective delta opioid receptor agonist [D-Pen2,D-Pen5] enkephalin and the selective kappa opioid receptor agonist U-69593 had no effect. In the presence of naloxone, which by itself had no effect on the release of radioactivity, the effect of [D-Arg2,Lys4]dermorphin-(1-4)-amide was abolished. These results show that the release of noradrenaline from periaqueductal gray slices is via a Ca(2+)-dependent exocytotic process, and that it is modulated through alpha 2-adrenoceptors as well as via mu-opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Stimulus-evoked release of tritiated monoamines from rat periaqueductal gray slices in vitro and its receptor-mediated modulation. 165 61

The electrically stimulated release of [3H]noradrenaline ([3H]NA) from slices of the nucleus tractus solitarii (NTS) from the rat in vitro was inhibited by the alpha 2-adrenoceptor agonist, clonidine, in a concentration-dependent manner and enhanced by the alpha 2-adrenoceptor antagonist, yohimbine. Phenylephrine, isoprenaline, carbachol, quinpirole and SKF 38393, all at 10(-6) M, did not affect the stimulus-evoked release of [3H]NA. The opioid peptides, alpha- and gamma-endorphin, did not have a significant effect on the stimulus-evoked release of [3H]NA; however, beta-endorphin reduced it in a concentration-dependent manner. [Leu5]Enkephalin also reduced [3H]NA release, but higher concentrations were necessary. The selective delta opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), as well as the selective kappa opioid receptor agonist, U-69593, were not effective. The selective mu opioid receptor agonist, [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO), concentration dependently reduced the stimulus-evoked release of [3H]NA to the same extent as beta-endorphin did. Naloxone, while having no effect on stimulus-evoked [3H]NA release, antagonized the effect of DAGO. These results corroborate that the release of NA from noradrenergic terminals in the NTS region of the medulla oblongata of the rat is modulated via alpha 2-adrenoceptors and suggest that the release of NA in the NTS in rats is also modulated via mu opioid receptors.
...
PMID:The electrically stimulated release of [3H]noradrenaline from nucleus tractus solitarii slices in vitro is modulated via mu-opioid receptors. 167 75

In vitro competition studies with rat brain were performed to systematically define the characteristics of the [3H]U-69,593 binding site and of the site selectively labeled by [3H]EKC (in the presence of U-69,593 and mu and delta blocking agents). The [3H]U-69,593 site has a binding selectivity profile that corresponds to that of the kappa opiate receptor. That is, all kappa compounds, regardless of chemical class, and dynorphin A, the putative endogenous ligand for kappa receptors, bind to the site with high affinities, whereas mu and delta ligands and nonopiate compounds do not. The agonists U-69,593, ICI 197,067 and U-50,488 and antagonist nor-binaltorphimine were found to have a useful degree of selectivity for the site. The [3H]EKC site has opiate receptor characteristics and appears to be the most abundant opiate receptor in rat brain, but its binding selectivity profile is not that of a kappa receptor. Instead, this non-mu, non-delta, non-kappa site has the pharmacological properties that correspond to those of the beta-endorphin-specific, epsilon receptor that has been hypothesized to exist for some time. We could not identify any compound that is selective for the putative epsilon site. Of the more than 50 compounds tested, all were either equally potent at the [3H]U-69,593 and [3H]EKC sites or were more potent at the [3H]U-69,593 site.
...
PMID:Affinity of drugs and peptides for U-69,593-sensitive and -insensitive kappa opiate binding sites: the U-69,593-insensitive site appears to be the beta endorphin-specific epsilon receptor. 216 90

We have reported previously that i.v.t. beta-endorphin increases the release of immunoreactive Met-enkephalin but not Leuenkephalin or dynorphins from the spinal cord. To determine if the effect is specific to beta-endorphin, the present investigation tested i.v.t. beta-endorphin, its analogs and other opiate agonists with different opioid receptor activities for their ability to release Met-enkephalin using an intrathecal perfusion technique. Human beta-endorphin and its analogs, human beta-endorphin-(1-30), -(1-29) and -(1-28) which have an identical amino acid sequence in the NH2-terminus showed reduced stepwise potencies in releasing Met-enkephalin. The results correlated well with their analgesic potencies. Des-Met5-camel beta-endorphin (64 micrograms i.v.t.) which does not have a complete sequence of Met-enkephalin in its NH2-terminus but still retains 20% of camel beta-endorphin analgesic potency caused the spinal release of Met-enkephalin. Morphine (mu opioid receptor agonist, 40 micrograms), D-Ala2-D-Leu5-enkephalin (delta opioid receptor agonist, 80 micrograms) and U-50488H (kappa opioid receptor agonist, 160 micrograms) injected i.v.t. were unable to cause any release of Met-enkephalin. High-performance liquid chromatography after Sephadex G-50 gel chromatography indicated that the immunoreactive Met-enkephalin in the spinal perfusate released by i.v.t. beta-endorphin had a retention time identical to authentic Met-enkephalin. Intraventricular injection of Met-enkephalin, 4 nmol (2.3 micrograms), caused little increase of Met-enkephalin immunoreactivity in the spinal perfusate, whereas 4 nmol of i.v.t. beta-endorphin caused a marked increase of Met-enkephalin in the spinal perfusate. Inhibition of peptidase by i.v.t. aprotinin and bacitracin does not prevent the spinal release of Met-enkephalin induced by i.v.t. beta-endorphin. It is concluded that the release of Met-enkephalin was specific to beta-endorphin and the results were not due to cross-immunoreactivity of beta-endorphin or its metabolites.
...
PMID:Spinal release of immunoreactive Met-enkephalin by intraventricular beta-endorphin and its analogs in anesthetized rats. 242 Sep 69

Recent studies have shown that inhibitory feedback mechanisms regulate the release of the endogenous opioid peptides beta-endorphin (acting predominantly at mu opioid receptors in the brain), dynorphin (a kappa opioid receptor ligand) and [Met]enkephalin (a delta opioid receptor ligand) from the rat hypothalamus. By using specific antagonists of the various opioid receptor types, it is shown that the release of these peptides from hypothalamic slices in vitro is not only controlled by homologous (auto)-receptors, but that cross-regulation between the three neuronal opioid receptor types also occurs; thus, the delta receptor antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu increases the release of all three peptides, the mu receptor antagonist D-tetrahydroisoquinoline-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 increases that of beta-endorphin and dynorphin, and the kappa receptor antagonist nor-binaltorphimine increases that of dynorphin; all these effects occur in the presence of tetrodotoxin, indicating a presynaptic site of action. We propose the term "allelo-receptors" to describe this particular form of neuronal regulation in which an endogenous ligand, acting via its own specific receptor, also regulates the release of related peptides which activate different classes of opioid receptors.
...
PMID:Presynaptic auto- and allelo-receptor regulation of hypothalamic opioid peptide release. 257 Mar 78

In the rabbit iris sphincter muscle, transmural electrical stimulation produces cholinergic and substance P-ergic responses. In the present work, the effects of dynorphin-(1-13), an endogenous ligand of the kappa opioid receptor, on these two neurogenic responses were examined pharmacologically and the data compared to findings in case of other opioid agonists. Dynorphin-(1-13) (10(-7) to 10(-6) M) enhanced the cholinergic responses and attenuated the substance P-ergic response, in a concentration-dependent manner, and these actions of dynorphin-(1-13) were more apparent in the case of low-frequency stimulation. These effects of dynorphin-(1-13) were antagonized by naloxone (10(-5) M). Dynorphin-(1-13) had no effects on the responses to exogenously applied acetylcholine, carbachol and substance P. The augmenting effect on the cholinergic transmission was unique in kappa agonists, as the cholinergic responses were also augmented by other kappa agonists such as dynorphin-(1-17) and ethylketocyclazocine, but attenuated by other opioid agonists (Met-enkephalin, beta-endorphin and morphine) and not affected by SKF-10,047 and nalorphine. On the other hand, the substance P-ergic response was attenuated by all the opioids used. These results suggest that dynorphin-(1-13) presynaptically increases the release of acetylcholine from the parasympathetic postganglionic nerves and reduces the release of substance P from the trigeminal nerve, mediated by kappa type of opioid receptors.
...
PMID:Dual effects of dynorphin-(1-13) on cholinergic and substance P-ergic transmissions in the rabbit iris sphincter muscle. 257 68

Pentylenetetrazol (PTZ, 45 mg/kg, ip) impaired retention of a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 10 min after training, as indicated by retention performance 48 h later. The amnestic effect of PTZ was prevented by naltrexone (0.01 or 0.10 mg/kg, ip) administered after training, but prior to PTZ-treatment. On the contrary, neither naltrexone methyl bromide (0.01, 0.10, or 10.0 mg/kg, ip), a quaternarium analog of naltrexone, nor MR2266 (0.01 or 0.10 mg/kg, ip), a putative kappa opiate receptor antagonist, modified the behavioral effects of PTZ. On the other hand, the body seizures produced by PTZ were unaffected by any of the three opiate receptor antagonists that were given before the convulsant. Taken together, these results suggest that the effects of PTZ on retention are mediated, at least in part, by opioid peptides of central origin, and rules out a possible participation of opioid peptides derived from prodynorphin-precursor molecule. Administration of beta-endorphin (0.01 or 0.10 microgram/kg, ip) 10 min prior to testing attenuate the retrograde amnesia caused by PTZ. The effect of beta-endorphin was prevented by the simultaneous administration of naltrexone (0.10 mg/kg, ip) prior to testing. Naltrexone has no effect of its own upon retrieval. These results suggest that the impairment of retention induced by PTZ is probably due, at least in part, to a release of opioid peptides in the brain during the post-training period. PTZ given after training do not affect consolidation or memory storage, as mice thus treated may retrieve the learned information when they are submitted to an appropriate neurohumoral and/or hormonal state in the test session, that is, beta-endorphin injection. Therefore, the action of PTZ would be primarily at the level of the mechanism that make stored information available for late retrieval.
...
PMID:The impairment of retention induced by pentylenetetrazol in mice may be mediated by a release of opioid peptides in the brain. 282 89

Stress can induce a naloxone reversible and a naloxone non reversible analgesia according to its parameters. We showed that naloxone non reversible analgesia can be reversed by antagonists of the kappa opiate receptor and that naloxone reversible analgesia can be related to mu receptors and beta-endorphin, while the kappa receptor mediated analgesia can be related to dynorphin. We have also shown that the characteristics of the receptors might change in consequence to stress and that the analgesic responses might be modulated by benzodiazepine agonists and antagonists.
...
PMID:Endogenous opioids and their receptors in stress-induced analgesia. 285 67

These experiments were designed to identify brain sites at which opioids might act to influence ingestive behavior and to determine which opioid receptor types are involved. After food deprivation, rats were given microinjections of naloxone into several brain regions and food intake was measured. Injections into or near the paraventricular (PVN) or ventromedial (VMH) hypothalamic nuclei or the globus pallidus (GP) reduced food intake; injections into the striatum or lateral hypothalamus (LH) were ineffective. A second study examined the ingestive effects of roughly equimolar doses (1.43-1.75 nmol) of dynorphin A (DYN), beta-endorphin (beta-END), and D-Ala2,D-Leu5-enkephalin (DADLE) when injected into 4 different brain regions. Only DYN significantly increased food intake, and this effect was seen only with injections into the PVN and VMH. Beta-END stimulated water intake when injected into the PVN, VMH and GP but not the LH. Further studies indicated that with PVN injections, DYN was effective at a dose as low as 0.47 nmol, and that a higher dose of DADLE (4.39 nmol) did stimulate food intake. These studies support an important role for dynorphin and the kappa opioid receptor in the regulation of feeding and suggest that the opioid regulation of food and water intake can be differentiated both by sites of action and by effective agonists.
...
PMID:Opioid-induced feeding: localization of sensitive brain sites. 287 Jul 73


1 2 3 4 Next >>

---