Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two side-chain cyclic lactam analogues of the 4-11 fragment of alpha-melanocyte-stimulating hormone (alpha-MSH), Ac-[Nle4,D-Orn5,Glu8]alpha-MSH4-11-NH2 and Ac-[Nle4,D-Orn5,D-Phe7,Glu8]alpha-MSH4-11-NH2, were prepared on p-methylbenzhydrylamine resin by using a combination of N alpha-Boc and N alpha-Fmoc synthetic strategies with diphenyl phosphorazidate mediated cyclization. The melanotropin activities of these two analogues were examined and compared relative to those of alpha-MSH, Ac-[Nle4]alpha-MSH4-11-NH2, and Ac-[Nle4,D-Phe7]alpha-MSH4-11-NH2. In the frog (Rana pipiens) skin bioassay, the L-Phe7 17-membered ring cyclic analogue was slightly more potent than the linear Ac-[Nle4]alpha-MSH4-11-NH2 and exhibited prolonged melanotropic bioactivity (greater than or equal to 4 h). In this same assay, the D-Phe7 cyclic analogue was more than 100-fold less potent than the L-Phe cyclic analogue and was 10,000 times less potent than linear Ac-[Nle4,D-Phe7]alpha-MSH4-11-NH2. In the lizard skin (Anolis carolinensis) bioassay, the L-Phe7 cyclic analogue was 100-fold less potent than Ac-[Nle4]alpha-MSH4-11-NH2, while the D-Phe7 cyclic analogue was 10,000-fold less potent than both Ac-[Nle4]alpha-MSH4-11-NH2 and the D-Phe7 linear derivative Ac-[Nle4,D-Phe7]alpha-MSH4-11-NH2. The solution conformation of these two cyclic analogues in dimethyl sulfoxide-d6 was examined by 1D and 2D 500-MHz 1H NMR spectroscopy. Our analysis suggests an H bond stabilized C10 (or C13) turn for the D-Phe7 cyclic structure while the L-Phe7 analogue is more conformationally flexible.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cyclic lactam analogues of Ac-[Nle4]alpha-MSH4-11-NH2. 285 55

The purpose of this study was to compare the binding potency to opioid receptors of met-enkephalin-derived, hypophysiotrophic peptides with their reported growth hormone (GH)-releasing strengths in vitro and further, to determine the relative selectivity of each peptide for mu and delta opioid binding sites in the forebrain of the rat. A series of (GH)-releasing pentapeptides and hexapeptides (GHRP's), as well as rat (rGHRH) and human (hGHRH) growth hormone-releasing hormones were tested for preferential binding to specific opioid receptors. The site selectivity of each peptide was determined by its ability to compete for binding with synthetic ligands for mu (Tyr-D-Ala-Gly-MePhe-Gly-ol; DAGO) and delta ([D-Pen2,5]-enkephalin; DPDPE) opioid receptors. The various peptides differed in their selectivities for the two opioid receptors in that most of the GHRP's were mu-selective, while the naturally occurring GHRH's were delta-selective. Amidation of the C-terminal decreased delta selectivity. Besides affecting selectivity for the site, structural changes that enhanced GH-release by enkephalin-derived peptides also decreased their potency to compete for opioid binding sites. For example, dose-response curves for His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (SK&F 110679) inhibition of the binding of DAGO and DPDPE yielded IC50's of 6 and 20 microM, respectively. In contrast, Tyr-D-Trp-Gly-Phe-Met-NH2 (BI360), which is 1 X 10(3) times weaker than SK&F 110679 in releasing GH, had IC50's of 0.1 microM and 0.08 microM for inhibition of the binding of DAGO and DPDPE, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Binding of growth hormone-releasing hormones and enkephalin-derived growth hormone-releasing peptides to mu and delta opioid receptors in forebrain of rat. 285 11

The molluscan neuropeptide, Phe-Met-Arg-Phe-NH2 (FMRFamide), the mammalian opioid peptide met-enkephalin, and their common analogues, met-enkephalin-Arg6-Phe7 (YGGFMRF) and Tyr-Gly-Gly-Phe-Met-Arg-Phe-amide (YGGFMRFamide), were injected into the lateral ventricle of the rat; the cardiovascular effects were studied. FMRFamide caused a rapid, transient elevation in blood pressure accompanied by a great increase in pulse pressure. These effects were followed by secondary increases in blood and pulse pressures. Met-enkephalin produced an initial reduction in blood pressure which was followed by a gradual increase at the higher of two test doses (300 nmole). Injection of YGGFMRF resulted in a gradual increase in blood pressure. This response resembled that to met-enkephalin. The initial response to YGGFMRFamide was similar to that to FMRFamide: increases in both blood and pulse pressures after injection. However, the secondary effect of YGGFMRFamide, a prolonged reduction in blood pressure, was not produced by FMRFamide. These results suggest that the initial excitatory cardiovascular responses may be due to the presence of the C-terminal amide. All of the cardiovascular effects of injecting these peptides into the lateral ventricle were abolished by pre-treatment with naloxone in a dose that, itself, produced no cardiovascular changes. In conclusion, these peptides seem to act via the naloxone sensitive opiate receptors in the rat brain.
 ...
PMID:Cardiovascular effects of intraventricular injection of FMRFamide, Met-enkephalin and their common analogues in the rat. 286 Oct 46

In order to clarify the effects of endogenous opiate peptides on the vasopressin system, we have investigated the presence of different opiate receptor subtypes in the neurohypophysis by radioreceptor assay and autoradiography. [3H]-etorphine binding to membrane preparations revealed the presence of high- and low-affinity binding sites (KD, 1.2 nM and 8.1 nM). Displacement of [3H]-etorphine by opiate receptor subtype-specific ligands gave the following results: the preferential mu agonists DAGO (Tyr-D-Ala-Gly-NMe-Phe-Gly-oL) and the tetrapeptide morphiceptin did not displace etorphine; the preferential sigma receptor agonists DADLE (D-Ala2,D-Leu5-enkephalin) or DSTLE (D-Ser2,Leu5,Thr6-enkephalin) and beta-endorphin, a preferential agonist of the epsilon receptor, displaced [3H]-etorphine from its low-affinity site only, and dynorphin 1-8, a preferential kappa agonist, displaced [3H]-etorphine from its high-affinity binding site. Film autoradiography of neurohypophyseal sections incubated with [3H]-etorphine showed a displacement of 30% of the labeled ligand by unlabeled dynorphin 1-8. Exposure of rat neurointermediate lobes in organ culture to dynorphin 1-8 caused a small but significant stimulation of vasopressin release. These results demonstrate the existence of dynorphin 1-8 sensitive opiate receptors of the kappa subtype in the neurohypophysis and their possible involvement in vasopressin release.
 ...
PMID:Dynorphin 1-8 binds to opiate kappa receptors in the neurohypophysis. 287 1

The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly-Phe (-Met/-Leu at their amino-terminus. Three distinct families of these peptides (beta-endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). Met-enkephalin, Leu-enkephalin and the related heptapeptide Met-enkephalin-Arg6-Phe7 and octapeptide Met-enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structures of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. At the present time the main question concerns the physiological significance of such a great diversity of endogenous opioid peptides.
 ...
PMID:[Discovery, anatomical mapping and biosynthesis of various families of endogenous opioid peptides]. 287 7

In opiate-naive rats, the endogenous opioid peptides, beta-endorphin, dynorphin(1-13) and Met-Enk-Arg-Phe (MEAP) and the synthetic enkephalin analogue D-Ala2-D-Leu5-Enk (DADLE) potently stimulated plasma corticosterone in a dose-dependent, naloxone reversible manner. To characterize their in vivo affinities, the effects of these peptides on plasma corticosterone release were tested in rats made tolerant to morphine, U50488H, DADLE/morphine or beta-endorphin. These cross-tolerance studies showed that dynorphin and MEAP exerted their action on plasma corticosterone release at kappa-opioid receptors. The action of DADLE occurred at delta-opioid receptors, while the action of beta-endorphin occurred principally at another receptor site. These results indicate that there is independent modulation of the hypothalamic-pituitary-adrenal axis by endogenous opioid peptides at mu-, delta- and kappa-opioid receptors. In addition there may be modulation by beta-endorphin at a separate site that we suggest could be a central epsilon-receptor site. This cross-tolerance paradigm, using a neuroendocrine model, provides in vivo evidence for the action of centrally active endogenous opioid peptides at multiple and independent opioid receptors.
 ...
PMID:Mu-, delta-, kappa- and epsilon-opioid receptor modulation of the hypothalamic-pituitary-adrenocortical (HPA) axis: subchronic tolerance studies of endogenous opioid peptides. 289 74

Using a rat tail-flick analgesic assay that uses a cold water-ethylene glycol mixture (-10 degrees C) as the noxious stimulus, we have been able to demonstrate a dose-related, naloxone-reversible analgesic effect for dynorphin A (1-17), the proposed endogenous ligand for the kappa receptor. Male Sprague-Dawley rats were implanted surgically with cannulas in the right lateral ventricle at least 1 week before testing. Five microliters of either drug or saline, followed by a 3-microliter saline flush, were administered. Nociceptive threshold was measured as the latency for the rat to flick or remove its tail from the bath solution after immersion. Dynorphin produced a dose-related analgesia at doses of 1 to 50 micrograms i.c.v., reaching 100% maximum possible analgesia (compared to predrug base line) at the highest dose. We found similar dose-related analgesia when we tested the selective mu agonist [Try-D-Ala-Gly-NMe-Phe-Gly-ol] (0.01-1 microgram), the selective kappa receptor ligand U-50,488H (100-500 micrograms), the selective delta agonist [D-Pen2,5]-enkephalin (50-200 micrograms) and beta-endorphin (0.1-10 micrograms). Naloxone (1.0 mg/kg) was able to block the antinociceptive effect of all but the highest doses of dynorphin, which required 10.0 mg/kg of naloxone. When we compared the same dosages of dynorphin using hot water (55 degrees C) as the noxious stimulus, no antinociception was observed. Although we do not known the mechanisms responsible for the differences between the hot and cold water tests, it may be that the cold water tail-flick test, which is able to assess the antinociceptive activity of both opioid agonists and mixed agonist-antagonists, is a more sensitive measure of the type of analgesia mediated by kappa receptors.
 ...
PMID:Antinociceptive action of intracerebroventricularly administered dynorphin and other opioid peptides in the rat. 290 Mar 24

The effects of somatostatin, cyclo(D-Trp-Lys-Thr-Phe-Pro-Phe) acetate, a somatostatin analog, neurotensin, and met-enkephalin were studied in the rabbit eye by measuring the intraocular pressure (IOP), aqueous humor protein concentration, ocular blood flow and the pupil diameter. Somatostatin or the analog injected intracamerally (10 micrograms/eye) and infused intra-arterially (0.6-4 micrograms/min) had no significant effect on the parameters studied in normal eyes. However, somatostatin and, particularly, the analog attenuated the miotic response to a standard nociceptive stimulus consisting of topical application of 1% neutral formaldehyde. The other component parts of the irritative response were not attenuated. Intracameral injection of 1-2 micrograms neurotensin caused vasodilation in the anterior segment of the eye, a slight increase in aqueous humor protein concentration, and some decrease in IOP. Intracameral injection of 1-50 micrograms met-enkephalin had no effect on the blood-aqueous barrier, IOP or the pupil diameter. Neither did this dose of met-enkephalin attenuate the miotic response to exogenous substance P. It seems likely that somatostatin and the somatostatin analog attenuate the miotic response to nociceptive stimuli by preventing the release of a substance, presumably substance P, from sensory nerves.
 ...
PMID:Effects of somatostatin, a somatostatin analog, neurotensin and met-enkephalin in the eye with special reference to the irritative response. 290 80

1. The changes in FMRFamide (Phe-Met-Arg-Phe-NH2) immunoreactivity in response to incubation in dopamine, serotonin, met-enkephalin, oxytocin, arg-vasopressin and FMRFamide were examined in the central nervous system of the snail, Achatina fulica. 2. When the central nervous system was cultured in medium which contained dopamine and in medium which contained serotonin, the number of immunoreactive neurons increased in the anterior part of the cerebral ganglion and decreased in the sub-esophageal ganglion. 3. When arg-vasopressin was added to the culture medium, the number of immunoreactive neurons increased in the pedal ganglion and decreased in the other sub-esophageal ganglion. 4. By contrast, when the central nervous system was cultured in medium which contained oxytocin, the number of immunoreactive neurons did not increase, but rather decreased, in each ganglion. 5. No changes in immunoreactivity were detected in the central nervous system when it was cultured in medium which contained FMRFamide. 6. It appears, from these results, that the production and release of FMRFamide from different neurons are differentially affected by the physiologically active substances tested.
 ...
PMID:Dynamics of FMRFamide immunoreactivity in response to physiologically active substances in the central nervous system of the snail, Achatina fulica. 290 40

D-phenylalanine, bacitracin and puromycin produce long-lasting, naloxone-reversible analgesia in mice. Analgesic potency parallels potency of these compounds as inhibitors of met-enkephalin degradation by mouse brain enzymes. D-phenylalanine potentiates acupuncture analgesia in mice and humans and has been used to ameliorate a variety of human chronic pain conditions.
 ...
PMID:Analgesic properties of enkephalinase inhibitors: animal and human studies. 293 46


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