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

The aim of this study was to investigate further the influence of dermorphin (D), a new potent opioid peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), on the functional activity of the pituitary-adrenocortical system in man. Six normal men were treated with oral metyrapone to stimulate the secretion of ACTH, beta-lipotropin, and beta-endorphin. In these subjects, significant suppression of metyrapone-evoked release of ACTH and related peptides occurred during D infusion (5.5 micrograms/kg X min for 30 min) compared with that during saline infusion. These results indicate that D can induce a significant decline in plasma levels of ACTH, beta-lipotropin, and beta-endorphin, the major circulating peptides from the C-terminal part of proopiocortin, and suggest that opioid peptides may be involved in the control of the functional activity of pituitary-adrenocortical activity in man.
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PMID:Dermorphin reduces the metyrapone-evoked release of adrenocorticotropin, beta-endorphin, and beta-lipotropin in man. 299 56

Iodinated human beta-endorphin was affinity-cross-linked to opioid receptors present in membrane preparations from bovine frontal cortex, bovine striatum, guinea pig whole brain, and rat thalamus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography revealed covalently labeled peptides of 65, 53, 41, and 38 kilodaltons (kDa). The 65- and 38-kDa peptides were present in all four tissues. The 41-kDa peptide was seen only in bovine caudate and guinea pig whole brain while the 53-kDa peptide was absent in rat thalamus. All four labeled peptides were constituents of opioid receptors since their labeling was fully suppressed by the presence of excess opiates, such as bremazocine, during binding. The distribution and levels of the labeled species in the brain tissues examined and, in earlier work, in the neuroblastoma X glioma NG 108-15 cell line suggested that the 65-kDa peptide is a binding component of mu receptors while the 53-kDa peptide is a binding subunit of delta receptors. This result was strongly supported by the finding that the labeling of the 65-kDa peptide is selectively reduced by the presence of the highly mu-selective ligand Tyr-D-Ala-Gly-(N-Me)Phe-Gly-ol (DAMGE) during binding, while while the labeling of the 53-kDa peptide is selectively reduced or eliminated by the highly mu-selective ligand [D-Pen2, D-Pen5]enkephalin (DPDPE). The labeling of the 41- and 38-kDa bands was reduced by either DAMGE or DPDPE. The relationship of these lower molecular weight opioid-binding peptides to mu and delta receptors is not understood. Several possible explanations are presented.
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PMID:Identification of distinct binding site subunits of mu and delta opioid receptors. 300 57

Systemic injections of opiate agonists were made in male rats to elucidate the involvement of multiple opioid receptors in the stress response. As an index of activity in the hypothalamic-pituitary-adrenocortical axis, plasma corticosterone was measured by radioimmunoassay. Rats were injected with ethylketocyclazocine (EKC), U50488H, MR2034, bremazocine or tifluadom and sacrificed 1 hr later. These kappa agonists produced potent, dose-dependent, stereospecific increases in plasma corticosterone levels at doses far below those needed to elicit analgesia. These effects were reversed by opiate antagonists, naloxone or Win 44441-3, which by themselves caused dose-dependent decreases in plasma corticosterone. Animals made tolerant to the prototype kappa agonist, U50488H, showed an attenuated response to an acute injection of the drug. However, when animals made tolerant to morphine were injected acutely with U50488H, the drug caused a dramatic increase in corticosterone levels. In hypophysectomized rats, U50488H and L-EKC did not increase plasma corticosterone. The agonist/antagonists, butorphanol and cyclazocine, when injected, behaved like kappa agonists and increased plasma corticosterone levels potently. The mu opiates, morphine and etorphine, also had similar effects but were less potent and efficacious than the kappa agonists. The delta agonist D-Ala-D-Leu enkephalin showed similar results, confirming a mu and delta opioid input into the hypothalamic-pituitary-adrenocortical axis. There were concomitant increases in plasma adrenocorticotropin in morphine-, D-Ala-D-Leu enkephalin-, L-EKC- and U50488H-treated rats which were also seen in adrenalectomized rats. D-EKC and D-cyclazocine, which bind to sigma sites, had no effect on corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kappa opiate agonists modulate the hypothalamic-pituitary-adrenocortical axis in the rat. 301 37

Light microscopic autoradiography was used to visualize the neuroanatomical distribution of rat brain delta opioid receptors. Slide-mounted sections of rat brain were labeled with [3H]-[2-D-penicillamine, 5-D-penicillamine]enkephalin([3H]DPDPE), a highly selective delta opioid agonist. Saturation isotherms of [3H]DPDPE binding to thaw-mounted brain slices gave a maximal number of binding sites of 79.9 fmol/mg of protein and an apparent dissociation constant (Kd) of 6.3 nM. DPDPE and met-enkephalin inhibited [3H]DPDPE binding with high affinity (lC50 values of 6.3 and 13.8 nM, respectively). Putative mu opioid receptor selective ligands such as morphine sulfate, Tyr-D-Ala-Gly-NMePhe-Gyl-ol and [N-MePhe3, D-Pro4]morphiceptin (PL017) were less potent inhibitors of [3H]DPDPE binding. The rat brain areas containing the highest densities of receptors were the claustrum, basolateral amygdaloid nucleus, the caudate-putamen and nucleus accumbens, the external plexiform layer of the olfactory bulb and the olfactory tubercle. Moderate receptor density was characteristic of the hippocampal formation in which grains were seen over the molecular layer of the dentate gyrus and stratum oriens (CA1), and of the different layers of cerebral cortex. Generally, low density of binding was found over the thalamus and the septal nuclei. Low specific binding was also seen in the cerebellum, medulla oblongata and in the dorsal horn of the spinal cord. There was little specific [3H]DPDPE binding over the white matter areas.
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PMID:Light microscopic autoradiographic localization of delta opioid receptors in the rat brain using a highly selective bis-penicillamine cyclic enkephalin analog. 301 47

The potent opiate radioligands [3H]etorphine, [3H]ethylketocyclazocine (EKC), and [3H]naloxone, bound specifically and saturably to a single class of membrane-binding sites in rat neurointermediate lobe (NIL), with Kd values of 3.7, 24, and 51 nM, respectively. In the hypothalamus (Ht), [3H]etorphine bound to specific and saturable sites with a Kd of 2.9 nM. Binding-inhibition studies with [3H]etorphine and unlabeled etorphine-HCl as well as [3H]EKC and unlabeled EKC, revealed high and low affinity binding sites in rat Ht and NIL as well as in the neural lobe of the bovine pituitary gland. [3H]naloxone also bound specifically to two classes of sites in Ht membranes, but to only a single class of low affinity sites in NIL membranes. Specific binding represented 80-90% of total [3H]etorphine binding, about 75% of total [3H]EKC binding, and 45-55% of total [3H]naloxone binding at 22 C in NIL and Ht, respectively. Relative binding potencies derived from Ki values for binding-inhibition studies of [3H]etorphine with opioid peptides and opiates were: NIL, etorphine-HCl greater than dynorphin A greater than naloxone-HCl greater than dynorphin-(1-9) greater than beta-endorphin much greater than alpha-neoendorphin approximately (Leu5)enkephalin approximately DAGO (Tyr-D-Ala-Gly-NMe-Phe-Gly-ol); Ht, etorphine HCl greater than naloxone-HCl greater than beta-endorphin greater than dynorphin A much greater than DAGO greater than morphiceptin much greater than (Leu5)enkephalin. Specific [3H]etorphine binding was also demonstrable after preincubation of NIL membranes with DAGO and (Leu5)enkephalin and after preincubation of Ht membranes with morphiceptin and (Leu5)enkephalin; such binding could be displaced by nonradioactive dynorphin A. In addition, [3H]etorphine binding to bovine neural lobe was displaceable by naloxone-HCl, with an ED50 of 43 nM. Specific ligands for sigma-opiate receptors, such as (+)SKF 10,047 (N-allylnorcyclazocine), phencyclidine (PCP), and (-)cyclazocine, displaced specifically bound [3H]etorphine and [3H]EKC from NIL membranes only at high (micromolar) concentrations. However, specific [3H]PCP sites were of higher affinity in NIL and Ht membranes, with similar Kd values of 102 and 190 nM respectively, and different concentrations (0.15 and 1.32 pmol/mg protein, respectively). These data have revealed several differences in the opiate-binding properties of rat Ht and NIL membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Opiate receptor subtypes in the rat hypothalamus and neurointermediate lobe. 303 71

The occurrence of cross-tolerance between morphine and met-enkephalin, and between morphine and DADL (D-Ala-D-Leu-enkephalin) in causing mydriasis in mice was studied. Morphine-tolerant mice treated with met-enkephalin or DADL intracerebroventricularly (ICV) showed marked reduction of the pupillary effect of the endopioids. Maximal mydriasis in tolerant animals was only about 30% for met-enkephalin and 50% for DADL, compared to levels in nontolerant animals. These results are among the first to demonstrate cross-tolerance between morphine and enkephalins in intact animals and may suggest involvement of multiple opiate receptor systems in producing mydriasis.
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PMID:Opioid mydriasis: cross-tolerance between morphine and enkephalins. 352 Jun 6

A previous report described the existence of substantial amounts of enkephalin immunoreactivity and the occurrence of nerve terminals containing an enkephalin-like material in the pars nervosa of rat pituitary. It was suggested that an enkephalin innervation of the pars nervosa originating from the magnocellular hypothalamic nuclei might regulate the secretion of neurohypophyseal hormones. The results of the present studies support this hypothesis, as we find that a stable enkephalin analogue (D-Ala 2,D-Leu5-enkephalin) inhibits the calcium-dependent release of vasopressin evoked by electrical stimulation of the rat pituitary stalk in vitro. A similar inhibition of the stimulus-evoked vasopressin release is caused by morphine and beta-endorphin, and the inhibitory effects of the enkephalin analogue can be reversed by naloxone. These findings suggest the possible existence of inhibitory opiate receptors on the terminals of vasopressin fibres in the pars nervosa.
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PMID:Opiate receptors influence vasopressin release from nerve terminals in rat neurohypophysis. 624 3

1 The action of morphine, naturally occurring and synthetic opiate peptides on [3H]-noradrenaline release induced by nerve stimulation was studied in the isolated nerve muscle preparation of the cat nictitating membrane under experimental conditions in which the alpha-presynaptic receptors were blocked by phentolamine 1 microM. 2 Morphine and the naturally occurring peptides: [Met5]-enkephalin, [Leu5]-enkephalin and beta-endorphin reduced 3H-transmitter overflow and responses to nerve stimulation from the cat nictitating membrane, effects which were completely antagonized by naloxone 0.3 microM. The relative order of potency for the inhibition of the stimulation-induced 3H-transmitter overflow at the level of the IC50 (microM) was as follows: [Met5]-enkephalin (0.020 microM) greater than or equal to [Leu5]-enkephalin (0.036 microM) > morphine (0.3 microM) > beta-endorphin (1 microM). 3 The synthetic opiate pentapeptides: BW 180 C (Tyr-D-Ala-Gly-Phe-D-Leu), and BW834 C (Tyr-D-Ala-Gly-pClPhe-DLeu), which are resistant to enzymatic degradation were more potent than the enkephalins in reducing the stimulation-evoked transmitter overflow from the cat nictitating membrane. On the other hand, the tetrapeptide BW832 C, which lacks the D-leucine terminal of BW180 C l was less potent than the enkephalins in inhibiting neurotransmission. 4 In the presence of phenoxybenzamine 1 microM, 3H-transmitter overflow was increased 8 fold and the inhibition of neurotransmission by methionine-enkephalin was not affected. Exposure to phenoxybenzamine 10 microM increased [3H]-noradrenaline overflow 15 fold and antagonized the effects of methionine enkephalin on transmitter release. 5 In the cat nictitating membrane the inhibitory presynaptic opiate receptors are different from the presynaptic alpha-autoreceptors which regulate the release of noradrenaline elicited by nerve depolarization through a negative feed-back mechanism.
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PMID:Pharmacological differentiation of presynaptic inhibitory alpha-adrenoceptors and opiate receptors in the cat nictitating membrane. 625 97

FK-33-824 (Try-D-Ala-Gly-MePhe-Met(O)ol) is a potent enkephalin analog which has been tritium labelled with a high specific radioactivity (41 Ci/mmole). The labelled drug exhibits specific and saturable binding to rat brain crude mitochondrial fraction. Specific binding is inhibited by low concentrations of morphine, levallorphan and beta-endorphin, suggesting that FK 33-824 [3H] binds preferentially to mu opiate sites. Binding studies at equilibrium and kinetics of formation and dissociation of the labelled ligand-receptor complex indicate that FK 33-824 [3H] binds to two classes of specific sites. Their affinities are distinguishable at 0 degree (KD = 1.3 and 5.8 nM) and very close to each other at 37 degree (KD = 1.9 nM).
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PMID:[Binding of a tritiated enkephalinergic analog (FK 33-824) to a mitochondrial fraction of rat brain]. 626 15

Treatment of the isolated mouse was deferens with the enzyme arylsulfatase (E.C. 3.1.6.1) had an effect on the ability of this tissue to respond to various opiates. It increased the IC50 values and slopes of their dose-response curve for enkephalins and their analogs, and shifted to the right the curves for FK33824, levorphanol and normorphine. There was no effect on the action of etorphine, beta-endorphin or dynorphin. With morphine there was a biphasic effect, IC50 values increasing at low enzyme concentrations and decreasing at high enzyme concentrations. A further comparison of arylsulfatase effects on morphine and on D-Ala-2-D-Leu5-enkephalin indicated that the morphine effect, unlike the D-Ala-2-D-Leu5-enkephalin effect, could not be reversed by washing and that morphine, unlike D-Ala2-D-Leu5-enkephalin, became much less sensitive to naloxone antagonism. The observed modifications in the shape of the dose-response curves indicate that the effect of the opiates in the mouse vas deferens is more complex than that expected through the occupation of a simple receptor. There is either more than one type of functional receptor for each agonist or only one receptor, which can interact with every drug in different ways; this complexity is discussed in terms of various possibilities, including fractional occupancy, positive cooperativity and multiple sites.
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PMID:Functional opiate receptor in mouse vas deferens: evidence for a complex interaction. 631 79


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