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)

We have investigated the pharmacological profile of the opioid stimulation of adenylate cyclase activity in rat olfactory bulb, in order to identify the opioid receptor subtype(s) involved in this response. The synthetic delta-selective agonists (D-Ala2)deltorphin I, (2-D-penicillamine,5-D-penicillamine)-enkephalin, and (D-Ser-Leu5-enkephalyl)-threonine were effective stimulators of the enzyme activity, with EC50 values of 6.7, 420, and 63 nM, respectively. A significant increase was also observed with the mu-selective agonists (N-methyl-Phe3,D-Pro4)-morphiceptin, dermorphin, and (D-Ala2-N-methyl-Phe4-Gly-ol5)-enkephalin (DAGO). The latter two agonists displayed biphasic concentration-response curves, with high affinity components accounting for 75-80% of the maximal responses. The kappa-selective agonists U-50,488 and U-69,593 were ineffective, whereas (D-Ala2)dynorphin A-1-11, dynorphin A, dynorphin A-1-13, and dynorphin A-1-6 acted with a rank order of potency consistent with their affinity for delta receptors. The stimulatory responses of Leu-enkephalin, beta-endorphin, dynorphin A, and delta-selective agonists were counteracted by naltrindole with pA2 values of 9.39-8.93, whereas naloxone was less potent (pA2 = 8.17-7.59). The kappa-selective antagonist norbinaltorphimine was the least potent. The inhibition by naltrindole and naloxone of DAGO stimulation showed biphasic curves, with 90% of the response being antagonized more potently by naloxone than by naltrindole. These results demonstrate that delta- and mu- but not kappa-opioid receptor subtypes stimulate basal adenylate cyclase activity in rat olfactory bulb.
 ...
PMID:Characterization of opioid receptors mediating stimulation of adenylate cyclase activity in rat olfactory bulb. 132 51

The effects of the infusion of ACTH1-24 and proopiomelanocortin on the denervated adrenal gland have been investigated in conscious 3-6 weeks-old calves by means of the adrenal-clamp technique. To prevent variation in the release of endogenous ACTH the pituitary stalk was cauterized during preparatory surgery. ACTH1-24 (5 ng/min per kg, i.v.) increased the output of cortisol from the adrenal by about 500 ng/min per kg body weight and this effect was rapidly reduced by simultaneous infusion of ovine proopiomelanocortin at 5 ng/min per kg. Release of met5-enkephalin and leu-enkephalin from the adrenal was reduced by ACTH1-24 (P less than 0.05) and this effect was enhanced significantly by additional infusion of proopiomelanocortin (P less than 0.02). However met5-enkephalin represented less than one-third of the met-enkephalin containing peptide released and the output of this pool was unaffected by infusion of ACTH. Proopiomelanocortin had no effect on met5-enkephalin production nor that of the total pool of met5-enkephalin containing peptides. It is concluded that ACTH reduced the quantity of pro-enkephalin processed to met5-enkephalin.
 ...
PMID:Inhibitory effects of proopiomelanocortin on cortical and medullary activity in the calf adrenal. 132 90

The mouse anterior pituitary-derived cell line AtT-20 has been widely used to study the biosynthesis and secretion of peptide hormones, such as ACTH, and peptide-processing enzymes, such as carboxypeptidase-E (CPE). Although AtT-20 cells do not express dynorphin (Dyn), previous studies using gene transfer have revealed that these cells are capable of processing pro-Dyn into peptides such as Dyn-B-13. A Dyn-converting enzyme (DCE) has been identified in AtT-20 cells; this enzyme processes Dyn-B-29 to Dyn-B-13. By several criteria, the enzyme activity secreted from AtT-20 cells is similar to the previously characterized enzyme activity in rat brain and bovine pituitary. In AtT-20 cells, the DCE activity and CPE activity are localized to a similar secretory compartment. Upon stimulation with a beta-adrenergic agonist, a phorbol ester, a calcium ionophore, or forskolin, the secretion of DCE activity was increased; this rise was parallel to the secretion of CPE activity and ACTH. These data suggest that DCE activity is in the regulated pathway of secretion. In AtT-20 cells treated with glucocorticoid for up to 7 days, cellular levels of beta-endorphin decreased to half the control levels. In contrast, the levels of DCE activity did not decline in response to this treatment, suggesting that the enzyme activity was not coregulated with the endogenous hormone. Taken together, the data presented here support a role for DCE in posttranslational processing of regulatory peptides.
 ...
PMID:Secretion and regulation of a neuropeptide-processing enzyme by AtT-20 cells. 132 23

While enkephalin and dynorphin peptides have been well characterized in the spinal cord, the cellular localization of beta-endorphin (beta E) and the processing of pro-opiomelanocortin (POMC) to beta E and other non-opioid peptides in the cord have not been extensively investigated. Other investigators have characterized the various beta E forms present in rat spinal cord regions. Previous studies have also suggested that spinal POMC content is entirely derived from supraspinal sources. However, high proportions of beta E precursors present in spinal cord sieving profiles led us to suspect the presence of POMC cell bodies intrinsic to the cord. In this study, we performed thoracic spinal cord lesions on a group of animals and demonstrated the persistence of about one-third of control levels of beta E immunoreactivity (beta E-IR) below the level of the lesions. We also characterized POMC processing in various regions of the spinal cord both before and after lesioning. These data suggested that there may be intrinsic POMC/endorphinergic neuronal systems in the spinal cord.
 ...
PMID:Beta-endorphin processing and cellular origins in rat spinal cord. 133 92

1. A short review is given of the chemical, physical, and pharmacological development of the idea that target cell lipid membranes may catalyze the interaction between regulatory peptides (or other pharmacologic agents) and their cell surface receptors. 2. The message-address and the membrane compartments concepts explain the observed correlations between the three-dimensional structures of peptides induced by a membrane surface and their preference for a certain receptor subtype. 3. Examples are given for opioid peptides (enkephalin, dynorphin, etc.), tachykinin peptides (substance P, neurokinin A, etc.), and melanocortin peptides (ACTH, alpha-MSH, etc.). 4. Relationships between the conformation of substance P induced by membrane association and that of a non-peptide substance P mimetic are discussed. Possible reasons for the difference between agonistic and antagonistic properties in the peptide field are revealed by this case.
 ...
PMID:How do peptides interact with lipid membranes and how does this affect their biological activity? 134 87

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.
 ...
PMID:Influence of opioids on CSF vasopressin concentration in newborn pigs. 134 99

Whereas endopeptidase 24.11 cleaves the Gly-Phe bond in both Met- and Leu-enkephalin, endopeptidase 24.15 rapidly converts dynorphin A1-8, alpha and beta-neoendorphin into Leu-enkephalin, and Met-enkephalin-Arg6-Gly7-Leu8 (MERGL) into Met-enkephalin. Inhibitors of both endopeptidase 24.11 and endopeptidase 24.15 each produce antinociception, and inhibitors of endopeptidase 24.11 increase the magnitude of enkephalin antinociception. The present study compared the central antinociceptive effect of an inhibitor of endopeptidase 24.15, N-[1-(R-S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) with one of endopeptidase 24.11 N-[1-(RS)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate (cFP-F-pAB) upon central opioid antinociception induced by MERGL, metenkephalin and dynorphin A1-8. cFP-AAF-pAB, but not cFP-F-pAB increased MERGL antinociception on the tail-flick and jump tests. In contrast, cFP-F-pAB, but not cFP-AAF-pAB increased met-enkephalin antinociception. Whereas central dynorphin A1-8 failed to induce antinociception itself, co-administration of cFP-AAF-pAB and dynorphin A1-8 increased nociceptive thresholds. This effect was not accompanied by motor dysfunction, but was blocked by systemic pretreatment with naloxone or central pretreatment with naltrexone or nor-binaltorphamine, but not beta-funaltrexamine. These data indicate that endopeptidase 24.15 may be responsible for the degradation of specific opioid peptides (e.g., MERGL, dynorphin), and that this process may prevent the full expression of their antinociceptive properties.
 ...
PMID:Endopeptidase 24.15 inhibition and opioid antinociception. 134 91

The relationship of age-dependent changes in concentrations of various opioid peptides in the brain and pituitary to the development of hypertension was studied in the spontaneously hypertensive rat (SHR). Normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats served as controls. Opioids determined were dynorphin A (1-8) [DN-A(1-8)], beta-endorphin (BE) and Met-enkephalin (ME). Three approaches were used: (1) temporal correlations of opioid concentrations with the onset of hypertension in 4-, 8-, 12- and 16-week-old rats; (2) study of opioid changes when hypertension development was prevented with antihypertensive drugs and (3) determination of possible opioid peptide changes in another rat model of hypertension, the deoxycorticosterone acetate (DOCA) + salt model. Opioid peptide concentration differences (SHR/WKY) found were as follows. There were much lower DN-A(1-8) levels in the SHR hippocampus and hypothalamus at all ages studied. At 12 and 16 weeks, coincidently with the onset of hypertension, lower levels of BE were found in the anterior lobe of the pituitary, but there were higher BE and ME levels found in the neurointermediate lobe (NIL). Prevention of hypertension in SHR by 8 weeks of oral therapy with guanethidine and hydralazine reversed the BE and ME changes in the NIL but not in the anterior lobe. There were no brain or pituitary changes in opioid peptide concentrations associated with DOCA-salt hypertension. The results are interpreted as supporting a role for altered concentrations of brain and pituitary opioids in the genesis of SHR hypertension.
 ...
PMID:Age-related changes in opioid peptide concentrations in brain and pituitary of spontaneously hypertensive rats. Effect of antihypertensive drugs and comparison with deoxycorticosterone acetate and salt hypertension. 135 4

Plasma levels of beta-endorphin, met-enkephalin and dynorphin were assessed in acute myocardial infarction (AMI) patients, with and without pain (group I: no pain, N = 12; group II: severe pain, N = 16). Plasma opioid peptide concentration was measured on admission to hospital (between 1 and 3 h after the myocardial infarction onset), at 7, 12, 24 h and at 2, 3 and 4 days. A transient increase in plasma beta-endorphin levels was found in AMI patients with severe pain, the levels normalizing within 12-18 h when pain had ceased. No changes in beta-endorphin concentration were observed in AMI patients without pain. Compared with healthy subjects, low levels of met-enkephalin were found in both groups of AMI patients throughout the study. Low levels of dynorphin were observed in patients with no pain while in the other patients initial low levels of dynorphin normalized when pain ceased. Blood pressure, heart rate and central venous pressure values were normal and did not correlate with plasma opioid levels. The results suggest that endogenous opioids do not affect pain in the early phase of myocardial infarction. The rise in beta-endorphin concentration observed in patients with severe pain seems to be induced by pain stress.
 ...
PMID:Plasma endogenous opioid levels in acute myocardial infarction patients, with and without pain. 135 15

Exogenous kappa-opioid agonists have been shown to produce peripheral antinociceptive effects in inflamed tissue. This study sought to determine whether endogenous kappa-receptor ligands are present at the site of inflammation. In Freund's adjuvant-induced hindpaw inflammation in the rat, we show, by immunohistochemistry, that dynorphin is detectable within inflammatory cells and in the cutaneous nerves in a similar distribution as calcitonin gene-related peptide, a specific marker for sensory neurons. These findings extend our previous observations in that not only beta-endorphin and Met-enkephalin (mu- and delta-receptor ligands), but also a preferential kappa-ligand is present within inflamed subcutaneous tissue.
 ...
PMID:Dynorphin, a preferential ligand for kappa-opioid receptors, is present in nerve fibers and immune cells within inflamed tissue of the rat. 135 8


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