RESUMO
BACKGROUND: Kisspeptin and its cognate receptor GPR54 are the central driving forces in the hypothalamus-pituitary-gonadal axis essential for sexual maturation and reproduction. Kisspeptin/GPR54 signalling stimulates gonadotropin-releasing hormone (GnRH) neurones and induces pulsatile GnRH release. The molecular signalling pathway by which kisspeptin stimulates GnRH neurones is currently under investigation. METHODS: Primary GnRH neurones were isolated from young adult rats and loaded with the calcium indicator Fura Red. Cytosolic calcium was measured while the cells were stimulated with kisspeptin. RESULTS: GnRH neurones show a maintained increase of cytosolic calcium upon stimulation with 100 nM kisspeptin-10. The calcium elevation was inhibited 30% by 1 µM tetrodotoxin, a voltage-gated sodium channel blocker, and 76% by 30 µM SKF96365, an inhibitor of receptor-mediated calcium entry. Furthermore, removal of extracellular calcium completely abolished the kisspeptin-induced calcium elevation. CONCLUSION: Our results suggest that the major part of the kisspeptin-evoked calcium signal is generated by an action potential-independent calcium influx, possibly through channels of the classical transient receptor potential type, with an additional influx through voltage-gated calcium channels activated by sodium action potentials.
Assuntos
Sinalização do Cálcio/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Neurônios/metabolismo , Proteínas Supressoras de Tumor/fisiologia , Fatores Etários , Animais , Sinalização do Cálcio/efeitos dos fármacos , Técnicas de Cultura de Células , Citosol/metabolismo , Hormônio Liberador de Gonadotropina/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Imidazóis/farmacologia , Kisspeptinas , Neurônios/efeitos dos fármacos , Ratos , Ratos Transgênicos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Tetrodotoxina/farmacologia , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/farmacologiaRESUMO
The danger of thoracic aneurysm rupture increases with the size of the aneurysm. We report on a 59-year-old man who developed a secondary aneurysm of the descending thoracic aorta within the residual type A dissection that was approximately 9-cm long and in which a contained rupture occurred. The patient died as a result of a massive hemorrhage during the anesthesiological preparation for emergency operation a short time after double-lumen intubation and commencement of controlled artificial ventilation. Autopsy revealed an atelectatic lower pulmonary lobe that had partially fused with the aneurysm. The fusion may have been so substantial that it may have acutely eliminated the covering of the contained rupture during artificial ventilation.