Disease relevance of Dermorphin

• Dermorphin-related peptides from the skin of Phyllomedusa bicolor and their amidated analogs activate two mu opioid receptor subtypes that modulate antinociception and catalepsy in the rat [1].
• N-methyl-atropine reversed the severe bradycardia induced by dermorphin and completely prevented this phenomenon if given as pretreatment [2].
• A withdrawal contracture to the selective mu antagonist, cyprodime, after repeated exposures to a selective mu agonist, dermorphin, was restored by nor-binaltorphimine (BNI), a selective kappa antagonist [3].
• Dermorphin at 1 nM increased respiratory rate but caused hypoxia, acidosis and hypercapnia; at 50 nM, respiratory rate was suppressed [2].
• The selective benzodiazepine antagonist flumazenil (5 mg/kg), which has been shown previously to antagonize catalepsy and respiratory depression produced by relatively high doses of dermorphin, did not antagonize the respiratory or locomotor stimulant effect of dermorphin [4].

Psychiatry related information on Dermorphin

• The selective opioid mu receptor agonist dermorphin increased the locomotor activity of rats dose dependently at 10 to 100 pmol/kg i.c.v. Respiratory rate, relative tidal volume and respiratory minute volume also increased unrelated to changes in locomotor activity [4].
• 4 Intracerebroventricular infusion of dermorphin induced development of tolerance and precipitation of withdrawal symptoms upon administration of naloxone [5].
• The involvement of mu-opioid receptors in memory retrieval was examined in mice by using Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog with high affinity for mu-opioid receptors, and passive avoidance learning [6].
• Data are presented in this paper regarding the influence of the opioid peptide, dermorphin, and its conjugate on the conditioned reflex activity of sousliks [7].

High impact information on Dermorphin

• The predicted amino acid sequences of these precursors contained homologous repeats of 35 amino acids that included one copy of the heptapeptide dermorphin [8].
• Complementary DNA (cDNA) libraries were constructed from frog skin messenger RNA and screened with a mixture of oligonucleotides that contained the codons complementary to five amino acids of dermorphin [8].
• The opioid receptor preference for dermorphin and several dimerized structural analogues was investigated using rat brain synaptosomes and correlated with the potencies of intracerebroventricularly administered dimeric dermorphin peptides to inhibit gastric acid secretion [9].
• Dimeric dermorphin analogues as mu-receptor probes on rat brain membranes. Correlation between central mu-receptor potency and suppression of gastric acid secretion [9].
• Prolactin-releasing activity of dermorphin, a new synthetic potent opiate-like peptide, in normal human subjects [10].

Chemical compound and disease context of Dermorphin

• Acid secretion from the gastric fistula stimulated by pentagastrin was enhanced by dermorphin, inhibited by DADLE and unaffected by dynorphin-(1-13) [11].
• Acid secretion stimulated by 2-deoxy-D-glucose from the gastric fistula was not modified by dermorphin and dynorphin-(1-13), while DADLE significantly inhibited it; at the same time gastric secretion from the Heidenhain pouch was significantly increased by dermorphin and unmodified by DADLE and dynorphin-(1-13) [11].
• When incorporated into dermorphin or deltorphin II, the Tic and Htc analogues all showed a large decrease in both mu and delta affinities and activities [12].
• SK&F 86466 dose-dependently reversed the dermorphin-induced depression of ventilatory parameters, while SK&F 86466 exerted no effect on dermorphin-induced analgesia or depression of locomotor activity due to catalepsia [13].

Biological context of Dermorphin

• Structure-activity relationship of dermorphin on gastric secretion [14].
• In addition, like other opioid peptides, dermorphin and hyp6-dermorphin inhibit the elevation by prostaglandin E1 (PGE1) of the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) (IC50 values 0.2 micro M and 0.4 micro M, respectively) [15].
• Cell proliferation, measured as [(3)H]-thymidine incorporation and proliferating cell nuclear antigen immunostaining, was stimulated by DADTII and inhibited by dermorphin [16].
• Dermorphin induced less clear changes in heart rate (maximum increase of 39 +/- 14 beats/min at the dose of 1 pmol) [17].
• Dermorphin, at doses of 0.1-100 nmol/kg, increased blood pressure and hindquarter blood flow, renal and mesenteric resistance, and core temperature [18].

Anatomical context of Dermorphin

• H-Tyr-D-MetO-Phe-Gly-NH2 (I) (guinea pig ileum IC50 = 13.6 nM; tail-flick ED50 = 1.97 pmol/mouse, icv, and 0.65 mumol/kg, sc), though less effective in the periphery, has central activities higher than those of dermorphin H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2 [19].
• Select types of opiates are known to release GH by a hypothalamic site of action, and thus, the dermorphin heptapeptide and benzomorphan opiate agonist 2549 used in this study presumably act on the hypothalamus to release GH [20].
• The purpose of this study was to clarify the mechanism of the blood-brain barrier (BBB) transport of H-Tyr-D-Arg-Phe-beta-Ala-OH (TAPA), which is a novel dermorphin analog with high affinity for the micro 1-opioid receptor [21].
• On the vas deferens receptors, dermorphin was about as potent as the enkephalins and 40 times more potent than morphine [5].
• Electrophysiological effects of dermorphin on locus coeruleus neurons of rat [22].

Associations of Dermorphin with other chemical compounds

• In the present paper we describe the synthesis of some dermorphin and deltorphin analogues beta-O- and alpha-C-glycosylated on the C-terminal amino acid residue and report their opioid receptor affinity and selectivity as well as their analgesic potency after subcutaneous injection in mice [23].
• We examined the in vitro and in vivo bioactivities of several families of peptidomimetic opioids including: constrained linear enkephalin (n = 12 analogs), dermorphin (n = 9 analogs) and morphiceptin (n = 17 analogs) [24].
• 3. The different mu-opioid agonists evaluated, morphine, DAMGO, dermorphin and [Lys(7)]-dermorphin produced an inhibitory response in vas deferens from wild-type mice but had no relevant activity on vas deferens from mutant mice [25].
• Acetylation of sugar hydroxyl groups reduces 5-10 times both biological activity on GPI and mu-receptor affinity, whereas the antinociceptive potency was equal to (i.c.v.) or only two-three times lower (s.c.) than dermorphin potency [26].
• Both dermorphin and fentanyl showed more potent activity in younger pups than in older pups, possibly in the case of dermorphin because of developmental maturation of blood-brain barrier function [27].

Gene context of Dermorphin

• Prolactin and growth hormone responses to dermorphin in patients with prolactin-secreting pituitary adenoma [28].
• Somatostatin inhibits the dermorphin-stimulated thyrotropin release in man [29].
• It is proposed that dermorphin/2549 synergistically release GH with GHRP or GHRH because these opiates inhibit SRIF release [20].
• We have also demonstrated that another unnatural amino acid, 2',6'-dimethylphenylalanine (Dmp), is not only an excellent substitute for Phe at position 3 but also can mimic the aromatic N-terminal Tyr residue in a micro opioid receptor-selective dermorphin analogue (YRFB: Tyr-D-Arg-Phe-betaAla-NH(2)) [30].
• This study was designed to investigate the effect of dermorphin (D), a new synthetic potent opiate-like peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), on PRA, plasma aldosterone (PA), plasma cortisol (PC), and plasma ACTH levels in normal men [31].

Analytical, diagnostic and therapeutic context of Dermorphin

• To assess the validity of this model, we synthesized a series of dermorphin analogues carrying a net positive charge and tested them in mu- and delta-receptor representative binding assays and bioassays [32].
• Dermorphin analog Tyr-D-Arg2-Phe-sarcosine-induced opioid analgesia and respiratory stimulation: the role of mu 1-receptors [33]?
• Rats received a single microinjection of vehicle, saporin, dermorphin or dermorphin-saporin into the rostral ventromedial medulla and 28 days later, underwent either sham or spinal nerve ligation procedures [34].
• We have developed a specific enzyme immunoassay and used synthetic peptides to detect and purify the new predicted heptapeptide (2.4 micrograms/g dry skin) from the skin of the Phyllomedusa sauvagei frog from which dermorphin was originally isolated [35].
• Search for the structures initiating seizures triggered by intraventricular injection of the mu opioid agonist dermorphin in rats [36].

References