Adipokinetic Hormone/red Pigment-concentrating Hormone Research Articles

Neurochemical Effects of the Adipokinetic Hormone/Red Pigment Concentrating Hormone Family of Peptides in MK-801-Induced Schizophrenia Rat Model

Objective: Adipokinetic hormone (AKH) plays a role in sugar and lipid metabolism in insects. Previous studies of AKH showed memory improvements in a schizophrenia rat model that displayed memory impairment and reduced depression in a rat olfactory bulbectomy model. In this study, we investigated the effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on brain neurotransmitter levels and brain neurochemistry in a schizophrenia rat model. Materials and Methods: We administered AKH/RPCH peptides for 4 days sub-chronically, both in naive rats and also in the MK-801-induced schizophrenia rat model. Liquid chromatography-mass spectrometry apparatus was used for targeted and untargeted analysis of rat neurochemistry. Results: Increased brain glutamate levels characteristic of MK-801 peptide-treated rats were significantly reduced by AKH. Furthermore, AKH also increased brain dopamine levels in both naive and MK-801 rats. Metabolomic studies have shown that AKH affects lipid and glutamate metabolism, while hypertrehalosaemic hormone plays a role in sugar metabolism and inflammation. Conclusion: According to our results, AKH might affect dopaminergic and glutamatergic systems and reverse the effects of MK-801, possibly affecting NMDA receptors.

Effects of adipokinetic hormone/red pigment-concentrating hormone family of peptides in olfactory bulbectomy model and posttraumatic stress disorder model of rats

One of the major neuropeptide groups in insects is adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides. AKH had improving effects on depression and anxiety in animal models and it may be a new treatment choice in these disorders. Aim of this study was to investigate effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH) and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on animal behavior in olfactory bulbectomy (OBX) model and in posttraumatic stress disorder (PTSD) model of Wistar-albino rats. Lia-AKH and Pht-HrTH significantly increased time spent in escape platform’s quadrant compared to sham control while Lia-AKH significantly increased time spent in escape platform’s quadrant compared to OBX controls in probe trial of Morris water maze (MWM). Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased immobility time compared to OBX controls in forced swimming test (FST). Pht-HrTH significantly increased %open arm time compared to OBX controls in elevated plus maze (EPM) test. Ani-AKH significantly increased %open arm entry compared to sham control while Ani-AKH and Pht-HrTH significantly increased %open arm entry compared to OBX controls in EPM. In PTSD study Ani-AKH and Lia-AKH significantly decreased immobility time compared to traumatized controls in FST. In acoustic startle reflex test, Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased average startle amplitude compared to non-traumatized controls in PTSD study. Metabolomic studies showed that AKH may affect glutamatergic and dopaminergic system and neurochemistry. In conclusion, AKH peptides had wide ranging effects on behavior and improved performance in OBX and PTSD models in rats.

Effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on MK-801-induced schizophrenia models.

The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI). In the AAPA task, Long-Evans rats were treated with Ani-AKH (2mg/kg), Lia-AKH (2mg/kg), Pht-HrTH (2mg/kg), MK-801 (0.15mg/kg), and the combination of MK-801 with the hormones subchronically. In the prepulse inhibition test, Wistar albino rats were treated with Ani-AKH (1mg/kg), Lia-AKH (1mg/kg), Pht-HrTH (1mg/kg), MK-801 (0.1mg/kg), or the combination of MK-801 with hormones acutely before the test. In our study, Ani-AKH (2mg/kg), Lia-AKH (2mg/kg), and Pht-HrTH (2mg/kg) reversed MK-801 (0.15mg/kg)-induced cognitive memory impairment effects in the AAPA task. Lia-AKH (1mg/kg) significantly potentiated the MK-801-induced PPI disruption, while Ani-AKH (1mg/kg) partially potentiated the impairment caused by MK-801, and Pht-HrTH did not modify the effect of MK-801. In conclusion, AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK-801.

Effects of Adipokinetic hormone/Red pigment-concentrating hormone (AKH/RPCH) family of peptides for uterus contraction

Effects of Adipokinetic hormone/Red pigment-concentrating hormone (AKH/RPCH) family of peptides for uterus contraction

Effects of Acute Administration of Adipokinetic Hormone on Depression, Anxiety, Pain, Locomotion and Memory in Mice

The neurosecretory cells in the corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosemic or hyperprolinemic depending on the insect in question. They are the Adipokinetic Hormone/Red Pigment-Concentrating Hormone (AKH/RPCH) family of peptides. The present study investigated the effects of acute administration of Locusta Migratoria (Locmi-AKHII) and Anax Imperator (Anaim-AKH) on depression, anxiety, pain (analgesy), locomotion and memory in mice in forced swimming (FST), elevated plus maze (EPM), hot plate, locomotor activity and passive avoidance tests. Both Locmi-AKH-II (4 mg/kg) and Anaim-AKH (0.25 and 0.50 mg/kg) decreased immobility time (in sec, s) in the FST test. Anaim-AKH (0.5 and 1 mg/kg) increased the percentage of time spent in open arms/total time spent and the percentage of the number of open arm/total arm entries in the EPM test. Anaim-AKH (1 and 2 mg/kg) significantly increased latency (s) (initial time passed) for mice to lick their hind paws or jumping in the hot plate test. Anaim-AKH (4 mg/kg) significantly decreased the total distance (cm) moved, or the speed (cm/s) of movement of the animals in the locomotor activity test. Neither Locmi-AKH-II nor Anaim-AKH altered the retention latency (s) in the passive avoidance test. Both Locmi-AKH-II and Anaim-AKH exerted antidepressant effects, while only Anaim-AKH had anxiolytic and analgesic effects when administered acutely. Anaim-AKH diminished locomotion at higher doses while Locmi-AKH-II had no such effects. Neither Locmi-AKH-II nor Anaim-AKH disturbed learning and memory when acutely administered. Data of our studies suggest clinical potentials of AKH to be used in depression, anxiety and pain without disturbing memory.

Functional Characterization of Hypertrehalosemic Hormone Receptor in Relation to Hemolymph Trehalose and to Oxidative Stress in the Cockroach Blattella germanica

Hypertrehalosemic hormone (HTH) is a peptide hormone that belongs to the adipokinetic hormone/red pigment concentrating hormone (AKH/RPCH) family, which exerts pleiotropic actions related to catabolic reaction and stress response. AKH peptides have been demonstrated to participate in stress response including oxidative stress in several insects. In order to study the signaling pathway of HTH involved in anti-oxidative stress, we have characterized a HIH receptor cDNA in Blattella germanica (Blage-HTHR) in structural and in functional terms using RNA interference (RNAi). Blage-HTHR is expressed in various female adult tissues (brain–CC–CA, ventral nerve cord, midgut, fat body, oviduct), but maximal expression is observed in the fat body. RNAi-mediated knockdown of Blage-HTHR expression results in a significantly lower level of hemolymph trehalose, even though HTH is exogenously administered. Paraquat elicits lethal oxidative stress in B. germanica, and co-injection of paraquat and HTH reduces this detrimental effect and extends the median survival time. Interestingly, the “rescue” effect of HTH on mortality caused by paraquat is diminished in specimens with depleted expression of Blage-HTH and Blage-HTHR. Finally, lipid peroxidation in the hemolymph increases 4 h after paraquat treatment, in comparison with control specimens or with HTH-treated specimens. However, lipid peroxidation induced by paraquat was not “rescued” by HTH in Blage-HTH and Blage-HTHR knockdown specimens. Our results demonstrate that HTH acts as a stress hormone mediating anti-oxidative protection in B. germanica, and that its receptor, Blage-HTHR, is essential for this action.

Vanessa cardui adipokinetic hormone (Vanca-AKH) in butterflies and a moth

Small neuropeptides of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family regulate energy metabolism in insects. Within lepidopterans, the nonapeptide Manduca sexta AKH (Manse-AKH) represents a widely occurring AKH, whereas the decapeptide Helze-HrTH (at first isolated from Heliothis zea) seems to be restricted to moths. Here we show that Vanca-AKH, a non-amidated undecapeptide which we recently found in the painted lady butterfly, Vanessa cardui, is also present in the retrocerebral complex of several other butterflies ( Danaus plexippus, Precis coenia, Aglais urticae) and a moth ( Spodoptera frugiperda). This study also demonstrates the power of modern nano-electrospray-quadrupole TOF tandem mass spectrometry in the sequence confirmation of peptides from minute amounts of small neuropeptides.

A possible molecular ancestor for mollusk APGWamide, insect adipokinetic hormone, and crustacean red pigment concentrating hormone.

Precursor structures of various members of the neuropeptide family adipokinetic hormone/red pigment concentrating hormone (AKH/RPCH) of mandibular arthropods and the APGWamide family of mollusks were compared. Amino acid alignments showed a common overall architecture (signal peptide, active peptide, related peptide), with a similar alpha helix-random coil secondary structure. DNA sequence alignments revealed close similarities between the genes encoding for the peptides of the two families. The APGWamide genes are larger than the AKH/RPCH genes. The sequence environment occupied by introns is similar in AKH/RPCH and APGWamide genes. Such similarities suggest that these peptide families might have been originated by gene rearrangements from a common ancestor having either an AKH/RPCH/APGWamide-like structure or both an AKH/RPCH-like and an APGWamide-like structures. In the former model, DNA fragments could have been gained when the ancestor evolved to mollusks and it could have lost nucleotides when the progression to mandibular arthropods took place. In the second model, AKH/RPCH-like structures could have been fused during evolution toward mandibular arthropods, whereas in mollusks they could have been lost with the possible amplification of the APGWamide-like structure. Loss of domains in exon 1 may have originated the signal peptide and the first codon of the active RPCH. In exon 2, loss of domains possibly determined the junctions of codons 2 to 5 with the loss of a APGWamide copy; exon 3 underwent fewer variations. The similarity of the mollusk APGWamide precursors is closer to that of the RPCH family than the insect AKH family, indicating an earlier evolutionary departure.

Hypertrehalosemic hormone in a cockroach: molecular cloning and expression

Hypertrehalosemic hormone (HTH) is a neuropeptide in the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family that stimulates the synthesis of trehalose, the main blood sugar of many insects. The preproHTH of the cockroach Blaberus discoidalis was cloned from the corpora cardiaca (CC), the endocrine source for HTH, and the deduced sequence and organization of preproHTH were compared with other AKH/RPCH precursors. PreproHTH mRNA was determined to be ∼0.5 kb in length as predicted by DNA sequence analysis. Northern blot analysis of the CC, ventral nerve cord, brain and fat body detected HTH-mRNA only in the CC. Levels of the HTH transcript in the CC were determined according to age, gender and mating. The HTH message was most abundant in the CC during the first several days of adult life in both sexes, then declined by 50% and were stable. HTH-mRNA levels in the CC did not respond to mating.

The revolution in insect neuropeptides illustrated by the adipokinetic hormone/red pigment-concentrating hormone family of peptides.

The last decade has seen a surge in the knowledge on primary structures of insect neuropeptides. Particularly successful were isolations and sequence determinations of more than 30 members of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides. This brief overview describes the techniques used to obtain data on purification and structure such as high performance liquid chromatography, Edman sequencing and mass spectrometry. Moreover, a short account on the precursors and on the multiple functions of the peptides of the AKH/RPCH family in various crustacean and insect species is given.

A unique charged tyrosine-containing member of the adipokinetic hormone/red-pigment-concentrating hormone peptide family isolated and sequenced from two beetle species

An identical neuropeptide was isolated from the corpora cardiaca of two beetle species, Melolontha melolontha and Geotrupes stercorosus. Its primary structure was determined by pulsed-liquid-phase sequencing employing Edman chemistry after enzymically deblocking the N-terminal pyroglutamate residue. The C-terminus was also blocked, as indicated by the lack of digestion when the peptide was incubated with carboxypeptidase A. The sequence of this peptide, which is designated Mem-CC, is pGlu-Leu-Asn-Tyr-Ser-Pro-Asp-Trp-NH2. It is a new member of the adipokinetic hormone/red-pigment-concentrating hormone (AKH/RPCH) family of peptides with two unusual structural features: it is charged and contains a tyrosine residue at position 4, where all other family members have a phenylalanine residue. Structure-activity studies in the migratory locust (Locusta migratoria) and the American cockroach (Periplaneta americana) revealed that the peptide was poorly active, owing to its structural uniqueness.

Physiological actions by hypertrehalosemic hormone and adipokinetic peptides in adult Blaberus discoidalis cockroaches

Members of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family characteristically cause metabolite mobilization by the insect fat body. The present study identified several additional physiological actions in adult Blaberus discoidalis cockroaches that were influenced by synthetic Blaberus hypertrehalosemic hormone (HTH) and other AKH/RPCH family peptides. HTH elevated blood carbohydrate by 4-fold and cytochrome heme a + b synthesis of fat body mitochondria by 3-fold. Both carbohydrate and heme synthesis were dose-responsive to HTH. Carbohydrate synthesis was 10 times more sensitive to HTH than heme synthesis. Heme synthesis was also stimulated by Periplaneta cardioacceleratory hormones (CAH)-I and -II and RPCH but not by AKH-I or -II, at the doses tested. HTH showed strong cardioexcitatory activity. Long-term treatment of decapitated female B. discoidalis with juvenile hormone analog (JHA = methoprene) stimulated by 2.6-fold the rate of synthesis of secreted fat body proteins. HTH enhanced the JHA-dependent export protein synthesis by 42% above that observed with JHA alone. SDS-PAGE demonstrated that JHA determined the nature of the newly synthesized polypeptides; HTH enhanced their synthesis rate. Neither AKH-I nor HTH affected protein synthesis when added directly to isolated fat body. These results demonstrate that peptides of the AKH/RPCH family have multiple physiological actions related to fat body energy metabolism.