Disease relevance of Deltorphin A

• Effect of deltorphin on pituitary-adrenal response to insulin-induced hypoglycemia and ovine corticotropin-releasing hormone in healthy man [1].
• Intrathecal administration of the selective delta opioid receptor agonist, D-[Ala(2), Glu(4)] deltorphin, dose-dependently reversed thermal hyperalgesia induced by CFA [2].
• Finally, it did not affect the naloxone contracture after exposure to deltorphin [3].
• Both deltorphin and SNC-80 concentration-dependently inhibited the production of p24 antigen, an index of HIV-1 expression [4].

Psychiatry related information on Deltorphin A

• The delta1-selective opioid receptor antagonist, 7-benzylidenenaltrexone (3.5 ng), and the delta2-selective opioid receptor antagonist, naltriben (19 ng), significantly antagonized the inhibitory effects of DPLPE (3 microg) and deltorphin (3 microg) on passive avoidance learning, respectively [5].
• The increased locomotor activity and rearing were dose-related over the range of 0.13 to 3.8 nmol/rat for [D-Ala2]deltorphin II (DADELT II) and 1.04 to 20.8 nmol/rat for deltorphin [6].
• In contrast, DPLPE (3 microg) or deltorphin (3 microg) did not markedly influence behavioral responses induced by electroshocks during training of passive avoidance learning [5].

High impact information on Deltorphin A

• Deltorphin transport across the blood-brain barrier [7].
• Amino acid sequences obtained from the cDNA libraries coincide with the observed dermorphin and deltorphin sequences, suggesting a stereospecific posttranslational amino acid isomerization of unknown mechanism [8].
• Efficacy of the KOR antisense ODN treatment was behaviorally evaluated by assessing the antinociceptive effects of peripherally administered kappa- (EMD 61, 753 and U 69,593), mu- (DAMGO) and delta- (deltorphin) ORAs in the formalin test [9].
• Reporter gene constructs were used to map this effect of deltorphin to the AP-1- and NF-AT/AP-1-binding sites of the IL-2 promoter [10].
• Furthermore, the fluorescent conjugates of dermorphin and deltorphin were biologically active as demonstrated by their ability to hyperpolarize locus coeruleus neurons (DERM-A488 or -BTR) and inhibit calcium currents in NG108-15 (DELT-A488) [11].

Chemical compound and disease context of Deltorphin A

• To determine the role of delta-opioid receptors in the modulation of hypothalamic-pituitary-adrenal activity, we studied in normal subjects the effect of the highly selective delta-opioid receptor agonist deltorphin (DT) on the secretion of ACTH, cortisol, and arginine vasopressin in response to insulin-induced hypoglycemia [1].
• 1. Following a 5 min in vitro exposure to morphine (1.3 x 10(-7) M), U-50,488H (2.5 x 10(-8) M) and deltorphin (1.6 x 10(-8)-6.5 x 10(-9) M), the rabbit isolated jejunum exhibited a precipitated contracture after the addition of naloxone (2.75 x 10(-7) M) [12].
• To test this hypothesis, DOR-Ju.1 cells, derived from Jurkat cells stably transfected with a cDNA encoding the neuronal DOR, were stimulated with deltorphin or benzamide, 4-[[2,5-dimethyl-4-(2-propenyl)-1-piperazinyl](3-methoxyphenyl)methyl]N- ,[2S[(S*),2alpha,5beta]]-(9Cl) (SNC-80) prior to the addition of HIV-1 [4].

Biological context of Deltorphin A

• Synthesis and structure-activity relationships of deltorphin analogues [13].
• We chemically synthesized and tested the affinity of enkephalin- and deltorphin-like peptides that contain a phosphorylation site at their C-terminus [14].
• In the present study, we evaluated the effect of the highly selective delta-opioid receptor agonist deltorphin on the LH and follicle stimulating hormone (FSH) responses to naloxone in six healthy fertile women during the luteal phase of the menstrual cycle [15].
• These findings suggest that the C-terminal amino acid sequence of dermenkephalin plays a role of delta-address which is specific to dermenkephalin itself, and is not additive with another delta selective ligand such as DPDPE [16].
• Molecular dynamics conformations of deltorphin analogues advocate delta opioid binding site models [17].

Anatomical context of Deltorphin A

• Stress-induced activation of sympathetic nervous system is attenuated by the delta-opioid receptor agonist deltorphin in healthy man [18].
• Naltrindole 10(-12) M abolished the antiproliferative effect of 10(-7) M deltorphin on CD4+ T cells [19].
• This effect was also observed when rabbit isolated jejunum was pretreated with deltorphin (a highly selective delta agonist) [20].
• The responses to dermenkephalin in the hamster vas deferens were increased by addition of peptidase inhibitors; the maximum effect was obtained with 3 microM thiorphan [21].
• To determine whether DORs expressed by T cells signal through the MAPKs, extracellular-regulated kinases (ERKs) 1 and 2, two delta opioid peptides, deltorphin and [D-Ala2,D-Leu5]-enkephalin (DADLE), were studied in Jurkat cells that had been stably transfected with DOR (DOR-Ju.1) [22].

Associations of Deltorphin A with other chemical compounds

• The analgesia produced by DAMGO and deltorphin is selectively blocked by naloxone (p < 0.05) and naltrindole (p < 0.05), respectively [23].
• Both (D-Ala2, Glu4) deltorphin (DELT), a delta 2 agonist, and [D-Pen2, D-Pen5] enkephalin (DPDPE), a delta 1 agonist, stimulated adenylyl cyclase activity in rat olfactory bulb in a concentration-dependent manner, DELT being 25-fold more potent than DPDPE [24].
• In contrast, addition of met-enkephalin or deltorphin to the anti-sense treated T cell cultures did not have any effect on T cell proliferation [25].
• Finally, g- is the preferential conformer in the side chain of Phe3 in both deltorphin-I and dermenkephalin [26].
• The important element that orients the N-terminal tyramine is the interaction of the N-terminal amino group, with the carboxyl group of Asp4 in deltorphin I and with Asp7 through His4 (as a triad) in dermenkephalin [27].

Gene context of Deltorphin A

• Recently we demonstrated the inhibitory action on Growth Hormone (GH) secretion of an opioid heptapeptide, deltorphin (DT), that is highly selective in binding delta-opioid receptors [28].
• Overall, the data collected demonstrate that the putative prodermorphin product Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 named dermenkephalin, behaves as a potent delta opioid agonist exhibiting high affinity and high selectivity for the delta opioid receptor [29].
• Substitution on the Phe3 aromatic ring in cyclic delta opioid receptor-selective dermorphin/deltorphin tetrapeptide analogues: electronic and lipophilic requirements for receptor affinity [30].
• Deltorphin showed a biphasic effect: 10(-11) M enhanced IL-2 secretion, whereas higher concentrations (10(-9)-10(-7) M) were inhibitory.(ABSTRACT TRUNCATED AT 250 WORDS)[19]
• Moreover, the delta-opioid receptor agonist, Deltorphin (1 microM), mimicked the effects as NPFF and also occluded NPFF's actions on synaptic currents [31].

Analytical, diagnostic and therapeutic context of Deltorphin A

• In addition, analysis of skin extracts by enzyme immunoassays coupled to high performance liquid chromatography separations revealed the presence of, besides dermenkephalin, novel dermenkephalin-related peptides, i.e. [L-Met2]dermenkephalin, dermenkephalin-OH, and [Met(O)6]dermenkephalin [32].
• The effect of deltorphin and DAME on secretion of the T cell growth factor, IL-2, was determined by ELISA analysis of supernatants obtained from CD4+ T cells after 48-hr culture [19].
• Both [(2S,3R)-beta-MePhe3]deltorphin and [(2S,3R)-beta-MePhe3] dermenkephalin are more selective, however, and interact essentially specifically with the receptor in the binding assays and bioassays [33].

References