Intracerebroventricularly injected nesfatin-1 activates central cyclooxygenase and lipoxygenase pathways.

Nesfatin-1 is a multifunctional neuropeptide having crucial autonomic roles. It is well known that nesfatin-1 collaborates with other central neuromodulatory systems, such as central corticotropin-releasing hormone, melanocortin, oxytocin, and cholinergic systems to show its autonomic effects. Central arachidonic acid cascade plays an important role to provide the homeostasis by exhibiting similar autonomic effects to nesfatin-1. Based on these similarities, the current study was designed to show the effects of intracerebroventricularly (ICV) injected nesfatin-1 on the hypothalamic arachidonic acid (AA) cascade. Immunochemistry and western blot approaches demonstrated that ICV administration of nesfatin-1 provokes an increase in the hypothalamic cyclooxygenase (COX) -1, -2 and lipoxygenase (LOX) protein expression. Moreover, the microdialysis study demonstrated that centrally injected nesfatin-1 increased the posterior hypothalamic extracellular AA products. In conclusion, these findings report that while nesfatin-1 is generating its autonomic effects, it also might be using central prostaglandins and leukotrienes by activating central COX and LOX pathways.

Obestatin and Ghrelin May Have a Complementary Function During Acute and Chronic Period in Mice.

Obestatin is described as an anorexigenic peptide, and has adverse effects of ghrelin. It has no inhibitory effects on acute/chronic food intake, and it has been reported by several researchers. The role of obestatin in metabolism is still not clear. In the present study, the purpose is to determine the effects of chronically administrated obestatin. For this purpose, (1 µmol/kg; i.p.) or ghrelin (1 µmol/kg; i.p.) and food restriction (24h fast:24h fed) on plasma obestatin, ghrelin, leptin, insulin, cholecystokinin (CCK) and glucose levels, and body weight gain were investigated for 14 days in mice. Additionally, mice were treated with acute ip (100 nmol/kg) injections of obestatin or ghrelin to investigate the food consumptions, plasma obestatin and ghrelin levels to determine unknown acute effects of obestatin. Plasma ghrelin levels increased significantly in obestatin administered mice when compared with the control group for chronic treatment. This increase is consistent with immunohistochemical findings which claim that the number of ghrelin and obestatin immunopositive cells in fundus tissue of stomach are considerably high in obestatin treated animals. Plasma obestatin and ghrelin levels has shown an increase endogenously in food restricted mice, but plasma leptin and insulin levels have been found to be lower compared to the control group. Acute administration of obestatin caused a decrease in plasma obestatin level at 60 min after injection and had no effect on the reduction of food intake in each treatment time. These results imply that obestatin may not itself be involved in the metabolism regulation; however, obestatin accompanied by ghrelin may play a role in the long-term regulation of metabolism.

Centrally administered CDP-choline induced cardiovascular responses are mediated by activation of the central phospholipase-prostaglandin signaling cascade.

The present study was designed to determine the involvement of central prostaglandin synthesis on the pressor and bradycardic effect of cytidine 5'-diphosphocholine (CDP-choline). Intracerebroventricular (i.c.v.) administration of CDP-choline was made and blood pressure and heart rate were recorded in male Sprague Dawley rats throughout this study. Microdialysis and immunohistochemical studies were performed to measure extracellular total prostaglandin concentration and to show cyclooxygenase-1 and -2 (COX-1 and -2) immunoreactivities, respectively, in the posterior hypothalamic area. Moreover, rats were pretreated (i.c.v) with mepacrine [a phospholipase A2 (PLA2) inhibitor], ibuprofen [a nonselective COX inhibitor], neomycine [a phospholipase C (PLC) inhibitor] or furegrelate [a thromboxane A2 (TXA2) synthesis inhibitor] 5 min prior to the injection of CDP-choline to determine the effects of these inhibitors on cardiovascular responses to CDP-choline. Control rats were pretreated (i.c.v) with saline. CDP-choline caused a dose- and time-dependent increase in blood pressure and decrease in heart rate. Immunohistochemical studies showed that CDP-choline increased COX-1 and -2 immunoreactivities in the posterior hypothalamic area. CDP-choline also elevated hypothalamic extracellular total prostaglandin concentration by 62%, as shown in microdialysis studies. Mepacrine or ibuprofen pretreatments almost completely blocked the pressor and bradycardic responses to CDP-choline while neomycine or furegrelate partially attenuated the drug-induced cardiovascular effects. The results suggest that CDP-choline may stimulate prostaglandin synthesis through the activation of PLA2, cyclooxygenases (COX-1 and -2) and prostaglandins and at least TXA2, may mediate the drug׳s cardiovascular effects.