Disease relevance of His-pro-dkp

• These data indicate that hyperglycemia causes a profound alteration in cyclo(His-Pro) concentration in the rat brain striatum [1].
• The level of cyclo(His-Pro) in sera of individuals with hypothyroidism, hyperthyroidism, or alcoholic cirrhosis was in the normal range, while patients with renal failure had approximately 3-fold elevated levels of the peptide [2].
• Amyotrophic lateral sclerosis: thyrotropin-releasing hormone and histidyl proline diketopiperazine in the spinal cord and cerebrospinal fluid [3].
• Because TRH [or its metabolite cyclo(His-Pro)] is believed to be an important hormone regulating appetite and metabolism, we also evaluated pyroglutamyl peptidase-II activity in 27 euthyroid patients with obesity [4].
• Antagonism of ketamine-induced anesthesia and hypothermia by thyrotropin releasing hormone and cyclo(His-Pro) [5].

Psychiatry related information on His-pro-dkp

• Role of endogenous cyclo(His-Pro) in voluntary alcohol consumption by alcohol-preferring C57BL mice [6].
• Influence of thyrotropin releasing hormone and histidyl-proline diketopiperazine on spontaneous locomotor activity and analgesia induced by delta 9-tetrahydrocannabinol in the mouse [7].
• Histidyl proline diketopiperazine (Cyclo [His-Pro]) in eating disorders [8].

High impact information on His-pro-dkp

• Inhibition of prolactin secretion by histidyl-proline-diketopiperazine [9].
• We hypothesize that the two peptides His-Pro DKP and thyrotropin-releasing hormone (TRH) have independent origins, since TRH is found in the B cells [10].
• Histidyl-proline diketopiperazine (His-Pro DKP) cells in the pancreas of human fetuses aged between 12 and 19 wk were localized by the indirect antibody-enzyme method on semithin sections [10].
• Histidyl-proline diketopiperazine (His-Pro DKP) immunoreactivity is present in the glucagon-containing cells of the human fetal pancreas [10].
• Neither TRH nor cyclo(His-Pro) was produced from TRH-Gly in the presence of alpha-amidating enzyme under the present conditions [11].

Chemical compound and disease context of His-pro-dkp

• Insulin injection normalized blood glucose level and prevented an increase in cyclo(His-Pro) concentration after hyperglycemia [1].
• Streptozocin-induced hyperglycemia caused a significant increase in cyclo(His-Pro) concentration in the striatum but not in the other brain regions, whereas TRH concentration in any brain region did not differ between control and hyperglycemic groups [1].
• For example, a) acute pretreatment of rats with increasing amounts of cyclo(His-Pro) produces a progressive decrease in ethanol hypothermia, and b) chronic cyclo(His-Pro) administration augments the development of tolerance to hypothermic effects of alcohol [12].

Biological context of His-pro-dkp

• Analysis of human sera drawn at 3-h intervals over a 24-h period suggested a circadian rhythm of cyclo(His-Pro) levels [2].
• These results suggest that cyclo(His-Pro) may play a potential role in the regulation of water intake in the rat brain [13].
• TRH caused an increase in mean arterial blood pressure (MAP) of about 1 to 2 kPa whereas cyclo(His-Pro) and acid-TRH had no effect on MAP [14].
• These findings indicate that specific binding sites for cyclo(His-Pro) in the rat liver have similar properties to the receptors for other polypeptides [15].
• Histidyl-proline diketopiperazine decreases food intake in rats [16].

Anatomical context of His-pro-dkp

• Our results show that (a) the same cells are positive for both His-Pro DKP and glucagon/glicentin, (b) His-Pro DKP immunoreactive cells possess extremely electron-opaque secretory granules, implying that these cells correspond to the A cells, and (c) His-Pro DKP immunoreactivity is found over the secretory granules [10].
• A determination of the regional distribution of thyrotropin-releasing hormone and histidyl-proline diketopiperazine indicated that both peptides are found in highest concentrations in pituitary and hypothalamus, but are detectable in other areas of brain as well [17].
• Incubation of TRH-Gly (pGlu-His-Pro-Gly), a TRH precursor, with brain hypothalamic cytosols caused significant formation of His-Pro-Gly followed by the generation of histidyl-proline diketopiperazine (cyclo(His-Pro)), whereas TRH was not formed [11].
• Cyclo(His-Pro), or histidyl-proline diketopiperazine, is a cyclic dipeptide endogenous to blood, cerebrospinal fluid (CSF), semen, brain, spinal cord, and gastrointestinal tract of humans [18].
• The ontogeny of TRH and of a proposed TRH metabolite, histidyl proline diketopiperazine (His-Pro DKP), was determined in the rat central nervous system and pancreas as a means of studying the interrelationship of these peptides [19].

Associations of His-pro-dkp with other chemical compounds

• The antinociceptive action of the 2 main metabolites of thyrotropin-releasing hormone (TRH), pyroglutamyl-histidyl-proline (TRH-OH) and histidyl-proline-diketopiperazine or cyclo(His-Pro), were studied using mechanical (Haffner's test) and chemical (phenyl-p-benzoquinone writhing test) stimuli [20].
• Intraventricular administration of histidyl-proline-diketopiperazine [Cyclo(His-Pro)] suppresses prolactin secretion and synthesis: a possible role of Cyclo(His-Pro) as dopamine uptake blocker in rat hypothalamus [21].
• The cyclo(His-Pro) binding of liver membranes was solubilized by digitonin and octyl-glucopyranoside [22].
• These data indicate that cyclo(His-Pro) binding of rat liver membranes is solubilized by digitonin and is a glycoprotein of Mr 200,000 [22].
• Antagonism of ethanol-induced decrease in rat brain cGMP concentration by histidyl-proline diketopiperazine, a thyrotropin releasing hormone metabolite [23].

Gene context of His-pro-dkp

• PRL synthesis was not affected by TRH-OH and cyclo(His-Pro) [24].
• While there is specific binding of TRH to receptors in GH cells, no such receptors for cyclo(His-Pro) are detectable [25].
• This is the first report in which the effects of cyclo(His-Pro) on GH synthesis in teleosts are demonstrated [24].
• Lack of effect of histidyl-proline diketopiperazine on basal level and TRH-induced response of cytosolic calcium concentration in rat lactotrophs [26].
• Histidyl-proline diketopiperazine [cyclo(His-Pro)] has recently been shown to inhibit prolactin (PRL) secretion in vitro and in vivo [26].

Analytical, diagnostic and therapeutic context of His-pro-dkp

• The subcellular and organ distribution and natural form of histidyl-proline diketopiperazine in rat brain determined by a specific radioimmunoassay [17].
• Gel filtration column chromatography was used to establish that cyclo(His-Pro)-like immunoreactivity was found not only in free form established to be identical to cyclo(His-Pro) by high pressure liquid chromatography analysis on reverse phase and cation exchange columns, but also in a fraction of about 100,000 mol wt [2].
• Oral administration of 0.76 +/- 0.13 mg/kg/day cyclo(His-Pro), a peptide exhibiting dopaminergic agonist-like properties, during neuroleptic withdrawal did not change the course of dopaminergic supersensitivity reversal [27].
• Intraventricular administration of cyclo(His-Pro) significantly reduced water intake in these rats in a dose-dependent fashion (3 X 10(-10) -3 X 10(-8) mole), whereas its intraperitoneal injection did not cause any effect on water intake [13].
• Histidyl-proline diketopiperazine suppresses prolactin secretion in human pituitary tumour cell cultures [28].

References