Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the first patient with a defect in the Na+-taurocholate cotransporting polypeptide SLC10A1 (NTCP), which plays a key role in the enterohepatic circulation of bile salts. The clinical presentation of the child was mild and the child showed no signs of liver dysfunction or pruritus despite extremely elevated plasma bile salt levels (>100-fold upper-limit of normal). A homozygous point mutation was found in the SLC10A1 gene (resulting in amino acid change R252H) and functional studies confirmed the pathogenicity of the mutation. This confirms the role of NTCP as the major transporter of conjugated bile salts into the liver as part of the enterohepatic circulation and shows that other transporters partly can take over its function, resulting in a relatively mild phenotype. This work was published previously in [Vaz et al.: Hepatology 2015;61:260-267] and supplemented with some follow-up information of the patient.
 ...
PMID:Extended Abstract: Deficiency of Sodium Taurocholate Cotransporting Polypeptide (SLC10A1): A New Inborn Error of Metabolism with an Attenuated Phenotype. 2824 72

Itch is an unpleasant skin sensation that can be triggered by exposure to many chemicals, including those released by mast cells. The natriuretic polypeptide b (Nppb)-expressing class of sensory neurons, when activated, elicits scratching responses in mice, but it is unclear which itch-inducing agents stimulate these cells and the receptors involved. Here, we identify receptors expressed by Nppb neurons and demonstrate the functional importance of these receptors as sensors of endogenous pruritogens released by mast cells. Our search for receptors in Nppb neurons reveals that they express leukotriene, serotonin, and sphingosine-1-phosphate receptors. Targeted cell ablation, calcium imaging of primary sensory neurons, and conditional receptor knockout studies demonstrate that these receptors induce itch by the direct stimulation of Nppb neurons and neurotransmission through the canonical gastrin-releasing peptide (GRP)-dependent spinal cord itch pathway. Together, our results define a molecular and cellular pathway for mast cell-induced itch.
 ...
PMID:Nppb Neurons Are Sensors of Mast Cell-Induced Itch. 3091 12

Itch is a somatosensory sensation that informs the organism about the presence of potentially harmful substances or parasites, and initiates scratching to remove the threat. Itch-inducing (pruritogenic) substances activate primary afferent neurons in the skin through interactions with specific receptors that converts the stimulus into an electrical signal. These signals are conveyed to the dorsal horn of the spinal cord through the release of neurotransmitters such as natriuretic polypeptide b and somatostatin, leading to an integrated response within a complex spinal interneuronal network. A large sub-population of somatostatin-expressing spinal interneurons also carry the Neuropeptide Y (NPY) Y1 receptor, indicating that NPY and somatostatin partly regulate the same neuronal pathway. This review focuses on recent findings regarding the role of the NPY/Y1 and somatostatin/SST2A receptor in itch, and also presents data integrating the two neurotransmitter systems.
 ...
PMID:Neuropeptide Y in itch regulation. 3166 51

Centrally administered bombesin induces scratching and grooming in rats. These behaviors were blocked by early benzomorphan kappa opioid receptor (KOR) agonists as reported by Gmerek and Cowan in 1984. This was the first evidence that KORs may be involved in the sensation of itch-like behaviors. Subsequent development of additional animal models for acute and chronic itch has led to important discoveries since then. For example, it was found that (a) gastrin-releasing peptide (GRP), natriuretic polypeptide b and their cognate receptors are keys for the transmission of itch sensation at the spinal cord level, (b) dynorphins (Dyns), the endogenous KOR agonists, work as inhibitory neuromodulators of itch at the spinal cord level, (c) in a mouse model for acute itch, certain KOR antagonists elicit scratching, (d) in mouse models of acute or chronic itch, KOR agonists (e.g., U50,488, nalfurafine, CR 845, nalbuphine) suppress scratching induced by different pruritogens, and (e) nalfurafine, CR 845, and nalbuphine are in the clinic or in clinical trials for pruritus associated with chronic kidney disease and chronic liver disease, as well as pruritus in chronic skin diseases.
 ...
PMID:Antipruritic Effects of Kappa Opioid Receptor Agonists: Evidence from Rodents to Humans. 3329 31


<< Previous 1 2 3