Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypocretins (Hcrts) are recently discovered peptides linked to the human sleep disorder narcolepsy. Humans with narcolepsy have decreased numbers of Hcrt neurons and Hcrt-null mice also have narcoleptic symptoms. Hcrt neurons are located only in the lateral hypothalamus (LH) but neither electrolytic nor pharmacological lesions of this or any other brain region have produced narcoleptic-like sleep, suggesting that specific neurons need to be destroyed. Hcrt neurons express the Hcrt receptor, and to facilitate lesioning these neurons, the endogenous ligand hypocretin-2/orexin B (Hcrt2) was conjugated to the ribosome-inactivating protein saporin (SAP). In vitro binding studies indicated specificity of the Hcrt2-SAP because it preferentially bound to Chinese hamster ovary cells containing the Hcrt/orexin receptor 2 (HcrtR2/OX(2)R) or the Hcrt/orexin receptor 1 (HcrtR1/OX(1)R) but not to Kirsten murine sarcoma virus transformed rat kidney epithelial (KNRK) cells stably transfected with the substance P (neurokinin-1) receptor. Administration of the toxin to the LH, in which the receptor is known to be present, eliminated some neurons (Hcrt, melanin-concentrating hormone, and adenosine deaminase-containing neurons) but not others (a-melanocyte-stimulating hormone), indicating specificity of the toxin in vivo. When the toxin was administered to the LH, rats had increased slow-wave sleep, rapid-eye movement (REM) sleep, and sleep-onset REM sleep periods. These behavioral changes were negatively correlated with the loss of Hcrt-containing neurons but not with the loss of adenosine deaminase-immunoreactive neurons. These findings indicate that damage to the LH that also causes a substantial loss of Hcrt neurons is likely to produce the multiple sleep disturbances that occur in narcolepsy.
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PMID:Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. 1154 37

The melanin-concentrating hormone and neuropeptide glutamic acid-isoleucine are expressed in neurons located mainly in the hypothalamus that project widely throughout the CNS. One of the melanin-concentrating hormone main targets is the medial mammillary nucleus, but the exact origin of these fibers is unknown. We observed melanin-concentrating hormone and neuropeptide glutamic acid-isoleucine immunoreactive fibers coursing throughout the mammillary complex, showing higher density in the pars lateralis of the medial mammillary nucleus, while the lateral mammillary nucleus showed sparse melanin-concentrating hormone innervation. The origins of these afferents were determined by using implant of the retrograde tracer True Blue in the medial mammillary nucleus. Double-labeled neurons were observed in the lateral hypothalamic area, rostromedial zona incerta and dorsal tuberomammillary nucleus. A considerable population of retrogradely labeled melanin-concentrating hormone perikaryal profiles was also immunoreactive to neuropeptide glutamic acid-isoleucine (74+/-15% to 85+/-15%). The afferents from the lateral hypothalamic area, rostromedial zona incerta and dorsal tuberomammillary nucleus to the medial mammillary nucleus were confirmed using implant of the anterograde tracer Phaseolus vulgaris leucoagglutinin. In addition, using double-labeled immunohistochemistry, we found no co-localization between neurons expressing melanin-concentrating hormone and adenosine deaminase (histaminergic marker) in the dorsal tuberomammillary nucleus. We hypothesize that these melanin-concentrating hormone projections participate in spatial memory process mediated by the medial mammillary nucleus. These pathways would enable the animal to look for food during the initial moments of appetite stimulation.
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PMID:Distribution of melanin-concentrating hormone neurons projecting to the medial mammillary nucleus. 1243 28

Based on the importance of tuberomammillary nucleus (TMN) as a target for feeding/arousal-related functions, we aimed in the present study to investigate hypothalamic neuronal origin of neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) fibers projecting to the histaminergic nucleus. In the first series of experiments, we examined NPY (or CART) fiber distribution within the boundary of adenosine deaminase (ADA)-immunoreactive (ir) TMN regions; extensive NPY (or CART)-ir axon terminals were observed in E4 (TMMd), E3 (TMMv), and E2 (TMVr) subdivisions. NPY varicosities co-contained vesicular GABA transporters (vGAT). CART boutons, however, contained either vGAT or vesicular glutamate transporters (vGLU), which suggested dual (or multiple) origins of CART fibers. Based on the previous observation on melanin-concentrating hormone (MCH)-ir neuronal elements in the TMN, their coexistence with CART peptide was examined in detail. In E4 subdivision, approximately 40.8% of MCH-ir somata co-contained CART, but the proportion was reduced to 24.1% in E3 region. In E2 and E1 (TMVc) regions, only MCH-ir axon terminals existed without any MCH-ir somata. In the second series of experiments, we investigated hypothalamic neuronal origin of NPY (or CART) fibers projecting to the TMN. The arcuate nucleus (Arc) was the sole source of hypothalamic NPY fibers projecting to the nucleus. In contrast, CART fibers in the TMN originated from the Arc as well as the other hypothalamic nuclei including the retrochiasmatic nucleus, paraventricular nucleus, lateral hypothalamus (LH), zona incerta (ZI), and dorsal hypothalamic area. Quantitative analysis showed that arcuate CART projection to the TMN occupied approximately 23.5% of the total hypothalamic CART input to the nucleus, while the rest originated mainly from the LH and ZI. The present observations suggested that the TMN might play a key role in energy balance and arousal, by receiving periphery-derived, first-order NPY (or CART) inputs from the Arc as well as second-order (and downstream) CART inputs from the other hypothalamic nuclei.
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PMID:Hypothalamic neuronal origin of neuropeptide Y (NPY) or cocaine- and amphetamine-regulated transcript (CART) fibers projecting to the tuberomammillary nucleus of the rat. 2792 37