RESUMEN
Epstein-Barr virus-immortalized B lymphoblasts obtained from hypertensive patients with enhanced Na+/H+ exchanger activity (HT cells) proliferate distinctly faster upon serum stimulation than those from normotensive controls with low exchanger activity (NT cells) (Rosskopf, D., E. Frömter, and W. Siffert. 1993. J. Clin. Invest. 92:2553-2559). Stimulation with platelet-activating factor (PAF) as well caused an enhanced proliferation of HT cells. In analyzing possible differences in signal transduction between the immortalized NT and HT lymphoblasts, we observed that cell stimulation with PAF and somatostatin caused a twofold higher increase in [Ca2+]i in HT than in NT cell lines. This difference was completely abrogated by pertussis toxin (PTX) treatment. Furthermore, PAF-stimulated formation of inositol 1,4,5-trisphosphate (IP3) was twofold enhanced in HT cell lines. On the other hand, PAF receptor density and affinity, total cellular phospholipase C activity, expression of PTX-sensitive G proteins, and control binding of the stable GTP analogue, guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), to membrane G proteins were not different in NT and HT cell lines. However, PAF- and mastoparan-stimulated binding of GTP gamma S to G proteins, which was fully PTX-sensitive, was 2.5-fold higher in HT than NT cell lines. These data suggest an enhanced receptor-mediated activation of PTX-sensitive G proteins despite unchanged receptor and G protein expression. Thus, this study not only suggests that enhanced signal transduction and cell proliferation are abnormalities in a certain group of patients with essential hypertension but also explains these findings as a result of an enhanced G protein activation in this common disorder.
Asunto(s)
Proteínas de Unión al GTP/metabolismo , Hipertensión/metabolismo , Linfocitos/efectos de los fármacos , Receptores de Superficie Celular , Receptores Acoplados a Proteínas G , Intercambiadores de Sodio-Hidrógeno/metabolismo , Animales , Fenómenos Fisiológicos Sanguíneos , Calcio/metabolismo , Bovinos , División Celular/efectos de los fármacos , Línea Celular Transformada , Activación Enzimática , Proteínas de Unión al GTP/antagonistas & inhibidores , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Herpesvirus Humano 4 , Humanos , Hipertensión/patología , Linfocitos/metabolismo , Toxina del Pertussis , Fosfatidilinositol Diacilglicerol-Liasa , Hidrolasas Diéster Fosfóricas/metabolismo , Factor de Activación Plaquetaria/farmacología , Glicoproteínas de Membrana Plaquetaria/metabolismo , Transducción de Señal/efectos de los fármacos , Somatostatina/farmacología , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
This study assesses driving behaviour and history of driving outcomes through a semi-structured interview in 27 clinically referred German adults with ADHD and 27 age-, gender- and education-matched non-ADHD controls. In nineteen of the ADHD-subjects a test battery of driving-related cognitive measures was performed (ART 2020) and re-assessed after at least six weeks of treatment with methylphenidate (n = 9) or after a six-week medication free period (n = 10).ADHD-subjects drove significantly more kilometres per year, were more often registered by traffic authorities and fined more frequently, were involved in more accidents and described their driving style as more insecure and hectic than controls. A high-risk driving group was delineated with 3-6 accidents per ADHD-subject. All results were controlled for intercorrelations with driving experience. Methylphenidate treatment resulted in improved information processing, e.g., better visu-motor coordination under high-stress conditions, improved visual orientation and sustained visual attention compared to baseline and our untreated control group.