Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucagon, secreted from pancreatic alpha-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10(-9) M, suppressed low-glucose-induced intracellular calcium ion ([Ca2+]i) oscillations in alpha-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E2) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified alpha-cells indicate that 17beta-E2, BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E2 are blocked by the G alpha i- and G alpha o-protein inhibitor pertussis toxin, by the guanylate cyclase-specific inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3',5'-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E2, BPA, and DES in pancreatic alpha-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid.
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PMID:Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans. 1607 65

Encephalopathies and neurological disorders are sometimes associated with respiratory tract infections caused by Bordetella pertussis. For these complications to occur cerebral barriers have to be compromised. Therefore, the influence of pertussis toxin (PT), a decisive virulence determinant of B. pertussis, on endothelial barrier integrity was investigated. Human brain microvascular endothelial cells cultured on Transwell filter devices were used as model for the blood brain barrier. PT, but not its B-oligomer, induced a reduction of the transendothelial resistance and enhanced the permeability for the protein marker horseradish peroxidase. Moreover, transmigration of human monocytes was also elevated suggesting a PT-associated enhancement of the diapedesis of blood leucocytes. Uptake and trafficking of PT was followed by electron microscopy via clathrin-coated pits and accumulation in lysosomes and microvesicular bodies. The breach in barrier integrity was accompanied by a transient disintegration of Golgi structures. Interestingly, PT-induced effects were only transient and restoration of barrier function was observed after 24 h. In summary, intoxication by PT causes a transient destruction of the cellular organization in human brain-derived endothelial cells resulting in a transient disruption of barrier functions. We suggest that these findings reflect early steps in the development of neurological disorders associated with pertussis disease.
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PMID:Pertussis toxin transiently affects barrier integrity, organelle organization and transmigration of monocytes in a human brain microvascular endothelial cell barrier model. 1700 84


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