Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephrogenic diabetes insipidus (NDI) is caused by the inability of renal collecting duct cells to respond to arginine vasopressin (AVP)/antidiuretic hormone (ADH). We present the case of a 7-year-old boy with a history of excretion of large amounts of dilute urine and polydipsia since infancy. The boy had several vomiting episodes with mild dehydration during the first 3 years of life. There was no evidence of headaches, dizziness or visual problems. He drinks between 2 and 3 L/day and has 24-hour diuresis of 2 liters, now. He has prepubertal appearance with appropriate weight [+0.85 standard deviation score (SDS)] and height (+0.15 SDS) for his age. His intelligence was also normal. The water deprivation test showed low urine osmolality after 8 hours of dehydration. After desmopressin administration, urine osmolality remained low. Serum osmolality was in the normal range for sex and age before and after desmopressin administration. This indicated a nephrogenic form of diabetes insipidus. Molecular analyses revealed a P286L [p.Pro(CCC)286Leu(CTC)] mutation in the AVPR2 gene, that was inherited from his mother. This patient is the first case with genetically confirmed X-linked inherited form of NDI in the Republic of Macedonia. Molecular analysis confirmed the clinical diagnosis and enabled genetic advice for this family.
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PMID:X-Linked Recessive form of Nephrogenic Diabetes Insipidus in a 7-Year-Old Boy. 2593 2

The human endolymphatic sac (ES) is situated in a duplicature of the dura in the posterior cranial fossa and constitutes a part of the inner ear. The sac possesses immunological capacities and is responsible for a major part of the trans-epithelial ion transport occurring within the inner ear, via molecular mechanisms similar to that of the kidney collecting duct epithelia. Dysfunction of the trans-epithelial ion transport has been hypothesized as the reason for the endolymphatic hydrops occurring in Menieres diseases. Thus, candidate drug selection for medical treatment of Menieres disease has been based on a potential capability of improving trans-epithelial ion transport. However, recent human studies seems to rule out diuretic therapy and The Committee for Medicinal Products for Human Use redrew the recommendation for trimetazidine (Vastarel) treatment in the management of Meniere disease in 2012. This leaves betahistine (Betaserc) as the only drug for potential prevention of the incapacitating attacks of dizziness, tinnitus and hearing loss. However, the histamine receptors targeted by betahistine have never been demonstrated in the human ES. Accordingly, this study aims to investigate the expression of histamine receptors of the human ES epithelium and sub-epithelial stroma. Following sampling of human endolymphatic sac tissue during translabyrinthine surgery, the expression of histamine receptor genes was determined by cDNA microarray analysis. Results were subsequently verified by immuno-histochemistry. The combined results of microarrays and immuno-histochemistry showed expression of the histamine receptor HRH1 in the epithelial lining of the ES, whereas HRH3 was expressed exclusively in the sub-epithelial capillary network. Receptors HRH2 and -4 were not expressed. The present data provide the first direct evidence of a molecular rationale for betahistine treatment in Menieres disease. A potential betahistine effect in Menieres disease may primarily be through the H3-receptor antagonism, leading to inhibition of vestibular neuro-transmission and central vaso-dilation. The H1-receptor localization in the ES epithelium suggests an immuno-regulatory effect.
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PMID:Expression of histamine receptors in the human endolymphatic sac: the molecular rationale for betahistine use in Menieres disease. 2620 13