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 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)
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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.
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PMID:Cardiovascular effects of intraventricular injection of FMRFamide, Met-enkephalin and their common analogues in the rat. 286 Oct 46

The analgesic activity of the prototypic opioid peptides for the mu (D-Ala2-Me-Phen4-Gly-ol5-enkephalin [DAGO]) kappa (Dynorphin 1-13), delta (D-Ala2-D-Leu5-enkephalin [DADLE]), or epsilon (beta-endorphin) receptor was assessed in a rat tooth pulp stimulation procedure. All opioid peptides tested and the opioid alkaloid U50, 488H (kappa receptor agonist) significantly elevated response thresholds. The rank order of potency based on the Minimum Effective Dose values was beta-endorphin greater than DAGO = dynorphin A (1-13) amide greater than DADLE greater than dynorphin A (1-13) greater than U50,488H. Based on absolute magnitude, the rank order of dose response slopes was DAGO greater than U50,488H greater than dynorphin A (1-13) amide greater than beta-endorphin greater than DADLE. Dynorphin A (1-13) produced the shallowest dose response slope and the magnitude of response threshold was the lowest for all compounds tested. Finally, the general conclusion that mu agonists are effective against noxious stimuli derived from thermal, chemical, and mechanical is extended by our data to include electrical sources derived from tooth pulp stimulation; kappa agonists are effective against noxious stimuli derived from chemical, mechanical, and electrical sources (tooth pulp stimulation) and delta agonists are effective analgesics against thermal, chemical and electrical stimuli (tooth pulp stimulation).
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PMID:Antinociceptive profiles of opioid peptide agonists in a rat tooth pulp stimulation procedure. 286 29

Developmental and long-term behavioral effects of perinatal injection of beta-endorphin (BE), CRF and Tyr-Pro-Leu-Gly-NH2 (Tyr-MIF-1) in male rats were investigated along with the possibility that opiate receptors may be altered by the injection of BE during this critical time. Daily injections of peptide were given to pregnant females (100 micrograms/rat) in the week before birth or to the offspring (50 micrograms/rat) of untreated mothers during the first week of life. Prenatal BE and CRF reduced body weight on day 1, in contrast to Tyr-MIF-1 which produced a significant increase over controls by day 7 as well as a slight but significant acceleration of eye opening. Among the postnatal treatments, CRF-treated animals showed the most dramatic changes. These included decreased body weight, accelerated eye opening, and, in adulthood, increased open field rearing behavior and a tendency for a monotonic body temperature response to low doses of morphine, in contrast to the biphasic response shown by controls. BE, when given to pregnant mothers, increased the number (Bmax) of [3H]naloxone-labeled (mu) receptors in whole brains of offspring assayed on day 14, but it did not significantly alter [3H]D-Ala-D-Leu-enkephalin-labeled (delta) receptors. In contrast, a significant decrease in both mu and delta receptors was observed on day 14 in rats given BE postnatally. These differences in receptors were no longer apparent in adulthood, and no significant differences in tail-flick response were detectable at this time. Nevertheless, some of the effects of these three peptides endured well beyond their presence, and for BE included changes in the number of opiate receptors.
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PMID:Developmental, behavioral, and opiate receptor changes after prenatal or postnatal beta-endorphin, CRF, or Tyr-MIF-1. 286 78

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.
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PMID:Dynorphin 1-8 binds to opiate kappa receptors in the neurohypophysis. 287 1

Since both aminopeptidases and angiotensin I-converting enzyme are reported to degrade circulating enkephalins, we have examined the degradation of low-molecular-weight opioid peptides by a vascular plasma membrane-enriched fraction previously shown to contain both angiotensin I-converting enzyme (EC 3.4.15.1) and aminopeptidase M (EC 3.4.11.2). Except for an enkephalin analog resistant to amino-terminal hydrolysis, [D-Ala2]enkephalin, the purified vascular plasma membrane preferentially degraded low-molecular-weight opioids by hydrolysis of the N-terminal Tyr-1--Gly-2 bond. Enkephalin degradation was optimal at pH 7.0 and was inhibited by the aminopeptidase inhibitors amastatin (I50 = 0.08 microM), bestatin (9.0 microM) and puromycin (80 microM). Maximal rates of hydrolysis, calculated per mg plasma membrane protein, were highest for the shorter peptides (18.3, 15.6 and 16.6 nmol/min per mg for Met5-enkephalin, Leu5-enkephalin and Leu5-enkephalin-Arg6, respectively) and decreased with increasing peptide length (0.7 nmol/min per mg for dynorphin (1-13)). No significant hydrolysis of beta- and gamma-endorphin was detected. Km values decreased significantly with increasing peptide length (Km = 72.9 +/- 2.7, 43.6 +/- 4.7 and 21.4 +/- 0.9 microM for Met5-enkephalin, Leu5-enkephalin-Arg6 and Met5-enkephalin-Arg6-Phe7, respectively). However, no further decreases were seen with even larger sequences, i.e., dynorphin(1-13). Other peptides hydrolyzed by the plasma membrane aminopeptidase (angiotensin III, kallidin and hepta(5-11)-substance P) inhibited enkephalin degradation in a competitive manner. Thus, localization, specificity and kinetic data are consistent with identification of aminopeptidase M as a vascular enzyme with the capacity to differentially metabolize low-molecular-weight opioid peptides within the microenvironment of vascular cell surface receptors. Such differential metabolism may play a role in modulating the vascular effects of peripheral opioids.
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PMID:Degradation of low-molecular-weight opioid peptides by vascular plasma membrane aminopeptidase M. 287 42

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.
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PMID:[Discovery, anatomical mapping and biosynthesis of various families of endogenous opioid peptides]. 287 7

Opioid peptides and opioid receptors are found in the hearts of various species. Opioid peptides were also shown to modulate norepinephrine inducing changes in atrial rate, in vitro. Since we have recently shown a predominance of kappa and delta receptors in the rat atria, we found it of interest to study the role of highly selective opioid agonists on spontaneous and sympathetically stimulated heart rate. The pithed, artificially ventillated rat was used in these studies. D-Ala2-D-Leu5-enkephalin (DADL), was used as an delta-agonist, D-Ala2-MePhe4-Gly-ol5-enkephalin (DAGO) as a highly selective mu-agonist; Dynorphin A (1-17) as a kappa-agonist and beta-endorphin (beta-END) as a mixed epsilon-delta-mu agonist. Naloxone was used as an opiate antagonist. None of the above opioid peptides changed the basal blood pressure and heart rate at 1-100 nmol/kg except Dyn A-(1-17) which produced a brief depressor response (-15 +/- 2 mmHg, p less than 0.01). Stimulation of the spinal cord (50 v, 1 msec, 1 Hz, 30 sec) produced consistant pressor and cardiac accelerating responses. None of the opioid peptides studied blocked or enhanced the increase in blood pressure or heart rate produced by spinal cord stimulation. The depressor effect of the high dose of Dyn A-(1-17) was not blocked by naloxone. These results suggest that mu, delta or kappa opioid receptors in the rat heart have no role in the regulation of basal or sympathetically driven heart rate. Our data also suggest no role for these opioid receptors in modulation of basal arterial tone or norepinephrine-induced arteriolar constriction.
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PMID:The effect of mu, delta, kappa and epsilon opioid receptor agonists on heart rate and blood pressure of the pithed rat. 288 Dec 24

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.
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PMID:Long-term hyperalgesia induced by neonatal beta-endorphin and morphiceptin is blocked by neonatal Tyr-MIF-1. 288 15

Neonatal mice, under fasting conditions, are susceptible to the development of lesions in the arcuate nucleus (AN) of the hypothalamus, with high doses of monosodium L-glutamate (MSG). Feeding of nutrients (e.g., sugars and L-amino acids) has been shown to have a protective effect against the development of these lesions. The purpose of these studies was to elucidate the mechanism of this protective effect. Histopathologic examination of lesions of the AN demonstrated that feeding of weaning mice before subcutaneous administration of toxic doses of MSG suppressed the development of these lesions, as compared to fasted controls. Similarly, the number of necrotic cells in the AN of neonates administered toxic doses of MSG subcutaneously was reduced when D-glucose and L-arginine were administered orally. Atropine obliterated the protective effect of D-glucose. Pretreatments consisting of gastric inhibitory polypeptide (GIP) + oral D-glucose had a protective effect of higher potency than GIP alone. Pretreatments with insulin, anorexigenic peptide (pyroGlu-His-Gly), cholecystokinin, glucagon, bombesin, and substance P (in decreasing order of effectiveness) demonstrated a protective effect against the AN lesion in neonates, whereas somatostatin and beta-endorphin had no effect. Results suggest that the protective effect of nutrients may in part be due to the stimulation of peptide hormone release during the postabsorptive phase. It is postulated that the effect of entero-pancreatic hormone, especially insulin, is to enhance the tolerance of AN neurons of neonatal mice to the toxic dose of L-glutamate.
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PMID:Mealing and related hormone release suppress hypothalamic lesions of neonatal mice by L-glutamate. 288 96


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