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)

Human placental villus tissue contains opioid receptors and peptides. Kappa opioid receptors (the only type present in this tissue) were purified with retention of their binding properties. The purified kappa receptor is a glycoprotein with an apparent molecular weight of 63,000. Two opioid receptor mediated functions were identified in trophoblast tissue, namely regulation of acetylcholine and hormonal (human chorionic gonadotrophin and human placental lactogen) release. Placental content of kappa receptors increases with gestational age. Term placental content of kappa receptors correlates with route of delivery (higher in those abdominally obtained). Opioid use and/or abuse during pregnancy affects placental receptor content at delivery, as well as its mediated functions. Opioid peptides identified in placental extracts were beta-endorphin, methionine enkephalin, leucine enkephalin and dynorphins 1-8 and 1-13. Dynorphin 1-8 seem to be the predominant opioid peptide present in placental villus tissue.
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PMID:Properties and functions of human placental opioid system. 130 34

This study was designed to determine the influence of opioids on periarachnoid cortical cerebrospinal fluid (CSF) vasopressin concentration in newborn pigs equipped with closed cranial windows. Topical dynorphin-(1-13) produced tone-dependent pial arterial responses (dilation during normotension, constriction when cerebrovascular tone was decreased by hypotension). Dynorphin-(1-13) increased periarachnoid cortical CSF vasopressin concentrations in both normotensive and hypotensive piglets (5 +/- 1, 11 +/- 1, and 233 +/- 27 microU/ml for control, 10(-10), and 10(-6) M dynorphin-(1-13) during normotension, respectively). Dynorphin-(1-8) and U 50488H, a purported selective kappa-opioid receptor agonist, produced similar tone-dependent responses associated with smaller increases in CSF vasopressin concentration. beta-Endorphin caused only cerebral vasoconstriction associated with modest increases in CSF vasopressin (3 +/- 1, 5 +/- 1, 9 +/- 2 microU/ml for control, 10(-10), and 10(-6) M beta-endorphin, respectively). In contrast, methionine enkephalin- and leucine enkephalin-induced dilations were not associated with changes in CSF vasopressin concentration. Naloxone (1 mg/kg i.v.) blocked both the opioid-induced vascular effects and associated changes in CSF vasopressin concentration. Naloxone also attenuated the increase in CSF vasopressin concentration in response to hemorrhagic hypotension. These data show that dynorphin- and beta-endorphin-induced cerebrovascular effects are associated with increased CSF vasopressin concentration. Furthermore, these data indicate that opioids could contribute to the increase in CSF vasopressin concentration observed in response to hemorrhagic hypotension.
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PMID:Influence of opioids on CSF vasopressin concentration in newborn pigs. 134 99

Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8 sequence) were examined in 43 children with severe, primary obsessive-compulsive disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were positively correlated with one of eight obsessive-compulsive disorder severity ratings and three of seven measures of improvement following 5 weeks of treatment with clomipramine hydrochloride. Arginine vasopressin concentration was significantly and negatively correlated with several ratings of obsessive-compulsive disorder symptom severity, while oxytocin concentration was positively correlated with depressive symptoms. The ratio of arginine vasopressin to oxytocin was also negatively correlated with obsessive-compulsive disorder and depressive symptoms. Comorbid affective disorder was associated with decreased arginine vasopressin concentrations, while concomitant anxiety disorder was associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing hormone were not significantly related to obsessive-compulsive disorder symptoms. These results seem to indicate that arginine vasopressin may be related to obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid might be associated with drug response.
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PMID:Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder. 137 Jan 97

Disturbances in hypothalamic beta-endorphin and dynorphin levels were investigated in non-fasted genetically obese (ob/ob) and homozygous lean mice at 14-15 weeks of age. Eight brain regions were microdissected from fresh, unfixed brain slices, and opioid peptide concentrations were determined in tissue micropunches by radioimmunoassay. A two-fold and five-fold increase in beta-endorphin levels in ob/ob versus lean mice were found in the ventromedial and dorsomedial hypothalamic nuclei respectively. Dynorphin levels were comparable between ob/ob and lean mice in the anterior, lateral, ventromedial and paraventricular hypothalamic areas, but a 5-fold increase in dynorphin concentrations was detected in the dorsomedial hypothalamic nucleus of the ob/ob mouse. These results demonstrate that increased concentrations of beta-endorphin and dynorphin occur in discrete hypothalamic nuclei, which are known to influence food intake and glucose homeostasis. This could signify an important central defect contributing to hyperphagia and glucoregulatory dysfunction in obese mice.
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PMID:Increased beta-endorphin and dynorphin concentrations in discrete hypothalamic regions of genetically obese (ob/ob) mice. 168 94

1. A sucrose-gap technique was used to investigate the neuromodulatory actions of enkephalins on non-adrenergic, non-cholinergic inhibitory junction potentials (IJPs) in the circular muscle of the human large intestine. 2. The native enkephalins, [Leu5]enkephalin (LENK) and [Met5]enkephalin (MENK) caused a concentration-dependent reduction in amplitude of IJPs without a significant effect on the smooth muscle membrane. 3. The actions of LENK and MENK were mimicked by the delta-selective opioid receptor agonists [D-Pen2, D-Pen5]enkephalin (DPDPE) and [D-Ala2, D-Leu5]enkephalin (DADLE). 4. The actions of LENK, MENK and DPDPE were antagonized to similar extents by the delta-selective opioid receptor antagonist ICI 174,864. 5. The mu-selective opioid receptor agonist [D-Ala2, Me Phe, Gly-ol5]enkephalin was approximately 100-fold less potent than any of the native or synthetic enkephalins at reducing the amplitude of the IJP. Dynorphin A and beta-endorphin both had very weak activity. 6. Responses to all of the agonists were inhibited by naloxone. The degree of antagonism of DPDPE or DADLE by naloxone (1 microM) was the same as that of LENK or MENK. 7. Neither MENK nor LENK affected hyperpolarization of the smooth muscle membrane induced by ATP or 5-hydroxytryptamine. Vasoactive intestinal polypeptide (1 pM-1 microM) did not produce any observable responses and this lack of reactivity was not affected by the enkephalins. 8. It is concluded that in the circular muscle of the human colon, LENK and MENK can act on prejunctional delta-opioid receptors to produce inhibition of non-adrenergic, non-cholinergic inhibitory neuromuscular transmission. Possible physiological significance of this prejunctional receptor is discussed.
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PMID:Enkephalins modulate inhibitory neuromuscular transmission in circular muscle of human colon via delta-opioid receptors. 196 52

Two peptide models of dynorphin A(1-17) have been synthesized. These peptides incorporate a minimally homologous substitute sequence for residues 6-17, including alternating lysine and valine residues substituting for the potential amphiphilic beta-strand structure in positions 7-15. Model 1 retains Pro10 from the native sequence, but model 2 does not. Compression isotherms of peptide monolayers at the air-water interface and CD spectra of peptide films adsorbed from aqueous solution onto siliconized quartz slides were evaluated by comparison to those of idealized amphiphilic alpha-helical, beta-sheet, and disordered peptides. Dynorphin A(1-17) was mostly disordered, whereas beta-endorphin was alpha helical. Dynorphin model 1 had properties similar to those of dynorphin A(1-17) at these interfaces, but model 2 formed strongly amphiphilic beta sheets. In binding assays to mu-, delta-, and kappa-opioid receptors in guinea pig brain membranes, model 1 reproduced the high potency and selectivity of dynorphin A(1-17) for kappa receptors, and model 2 was only 3 times less potent and less selective for these receptors. Both peptide models retained the high, kappa-selective agonist activity of dynorphin A(1-17) in guinea pig ileum assays, and like dynorphin A(1-17), model 1 had little activity in the rat vas deferens assay. In view of the minimal homology of the modeled dynorphin structures, these studies support current models of membrane-catalyzed opioid ligand-receptor interactions and suggest a role for the amphiphilic alpha-helical and beta-strand structures in beta-endorphin and dynorphin A(1-17), respectively, in this process.
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PMID:Peptide models of dynorphin A(1-17) incorporating minimally homologous substitutes for the potential amphiphilic beta strand in residues 7-15. 197 58

The major cystosolic aminopeptidase (alanylaminopeptidase) was purified to homogeneity from human cerebral cortex and the specificity of its actions on a series of Leu-enkephalin-related peptides of increasing chain length was determined. In each case, only the N-terminal Tyr-Gly bond was hydrolysed. Kinetic analysis of the data revealed that the specificity constant (kcat/Km;s-1M-1) falls with increasing chain length from a maximum of 13.6 x 10(4) for Leu-enkephalin (5 residues) to 5.8 x 10(2) for dynorphin (1-13). Dynorphin 1-17, while not being degraded itself acted as a competitive inhibitor (Ki = 2.7 microM) of the degradation of smaller peptides. Beta-endorphin was not hydrolysed by analylaminopeptidase, nor did it act as an inhibitor of the enzyme.
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PMID:Specificity of action of human brain alanyl aminopeptidase on Leu-enkephalin and dynorphin-related peptides. 256 98

Since opioid peptides and opiate receptors have been demonstrated in the pancreatic islets, we investigated the effects of beta-endorphin, met-enkephalin, and dynorphin A, on basal and stimulated insulin secretion in the mouse. Each of the three opioid peptides was injected intravenously (0.06-64 nmol/kg) alone or together with each of the three insulin releasing agents glucose (2.8 mmol/kg), carbachol (cholinergic agonist, 0.16 mumol/kg), or terbutaline (beta 2-adrenoceptor agonist, 3.6 mumol/kg). It was found that beta-endorphin, met-enkephalin, and dynorphin A were all without effect on basal plasma insulin levels, except a slight elevation by beta-endorphin induced at 2 min after its injection at 64 nmol/kg (to 41 +/- 2 microU/mL vs 28 +/- 4 microU/mL in controls; p less than 0.05). Glucose- and terbutaline-induced insulin secretion were inhibited by beta-endorphin at the lower dose levels of 0.25 (p less than 0.01) and 1 nmol/kg (p less than 0.05). This effect was counteracted by the opiate receptor antagonist naloxone (500 micrograms/kg). In contrast, beta-endorphin at the high dose levels of 16 and 64 nmol/kg augmented the glucose- and terbutaline-induced insulin secretion (p less than 0.05). Carbachol-induced insulin secretion was not affected by beta-endorphin at the lower dose levels but augmented by the peptide at 64 nmol/kg (p less than 0.01). Met-enkephalin inhibited glucose- (p less than 0.01) and terbutaline- (p less than 0.05) induced insulin secretion at the high dose rates of 16 and 64 nmol/kg, but the peptide was without effect on carbachol-induced insulin secretion. The inhibitory effects were counteracted by naloxone. Dynorphin A did not affect stimulated insulin secretion at any of the dose levels tested. In summary, in the mouse 1. beta-Endorphin at low dose levels inhibits and at high dose levels augments stimulated insulin secretion; 2. Met-enkephalin inhibits stimulated insulin secretion; and 3. Dynorphin A does not affect insulin secretion. It is suggested that the main influence of beta-endorphin and met-enkephalin under in vivo conditions in the mouse is to inhibit stimulated insulin secretion.
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PMID:Effects of beta-endorphin, met-enkephalin, and dynorphin A on basal and stimulated insulin secretion in the mouse. 257 36

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.
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PMID:Dual effects of dynorphin-(1-13) on cholinergic and substance P-ergic transmissions in the rabbit iris sphincter muscle. 257 68

Leu-enkephalin, leu-enkephalinamide, ala-leu-enkephalin, met-enkephalin and dynorphin-A[1-13] were administered in microinjection into one of the self-stimulation sites of SN-VTA or MFB-LH and the electrical self-stimulation (SS) of the injected site and of the second site was recorded. The study revealed that the leu-enkephalin and the leu-enkephalinamide inhibited the SS of SN-VTA and produced no effect on the SS of MFB-LH, when administered into these sites. The MFB-LH injection, however, facilitated the SS of SN-VTA. The effect of ala-leu-enkephalin injection in MFB-LH was similar to the above, but the effect of the injection in SN-VTA was different in that it caused the facilitation of its SS and not the depression as seen with leu-enkephalin. Met-enkephalin injections in the two regions caused no direct or indirect changes of the SS of the regions. Dynorphin injection in SN-VTA facilitated its SS, like the injection of ala-leu-enk, but dynorphin injections in MFB-LH produced no effects. The results essentially demonstrate the differences in the effects of the different opioids in the reward system of the SN-VTA, and it is discussed that these differences are probably due to the preferences in the types of the receptors upon which these opioids act in the SN-VTA neuronal organisation. The results also demonstrate the major difference in the organisation of the reward substrate of the MFB-LH from that of the SN-VTA, as the effects of the opioids in the MFB-LH are markedly different or none compared to the effects in the SN-VTA.
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PMID:Differential effects of opioid peptides administered intracerebrally in loci of self-stimulation reward of lateral hypothalamus and ventral tegmental area--substantia nigra. 285 95


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