Inhibition of central angiotensin responses by angiotensin type-1 receptor antibody.

Angiotensin type-1 receptor subtypes (AT1) are implicated in the physiological actions of angiotensin II in the brain. In the present study we used an AT1 receptor antibody and a polymerase chain reaction--synthesized AT1 receptor complementary DNA to show that the hypothalamus expresses significantly higher levels of AT1 receptor messenger RNA and protein compared with the brain stem. Intracerebroventricular injections of AT1-specific antibody blocks the dipsogenic and blood pressure responses induced by centrally injected angiotensin II. These results demonstrate the expression of AT1 receptor gene in the brain and that the AT1 receptor antibody is able to inhibit the physiological responses of angiotensin II mediated by the brain.</jats:p

Ghrelin agonists impact on Fos protein expression in brain areas related to food intake regulation in male C57BL/6 mice

International audienceMany peripheral substances, including ghrelin, induce neuronal activation in the brain. In the present study, we compared the effect of subcutaneously administered ghrelin and its three stable agonists: Dpr 3ghr ([Dpr(N-octanoyl)3] ghrelin) (Dpr - diaminopropionic acid), YA GHRP-6 (H-Tyr-Ala-His-DTrpAla-Trp-DPhe-Lys-NH2), and JMV1843 (H-Aib-DTrp-D-gTrp-CHO) on the Fos expression in food intakeresponsive brain areas such as the hypothalamic paraventricular (PVN) and arcuate (ARC) nuclei, the nucleus of the solitary tract (NTS), and area postrema (AP) in male C57BL/6 mice. Immunohistochemical analysis showed that acute subcutaneous dose of each substance (5 mg/kg b.w.), which induced a significant food intake increase, elevated Fos protein expression in all brain areas studied. Likewise ghrelin, each agonist tested induced distinct Fos expression overall the PVN. In the ARC, ghrelin and its agonists specifically activated similarly distributed neurons. Fos occurrence extended from the anterior (aARC) to middle (mARC) ARC region. In the latter part of the ARC, the Fos profiles were localized bilaterally, especially in the ventromedial portions of the nucleus. In the NTS, all substances tested also significantly increased the number of Fos profiles in neurons, which also revealed specific location, i.e., in the NTS dorsomedial subnucleus (dmNTS) and the area subpostrema (AsP). In addition, cells located nearby the NTS, in the AP, also revealed a significant increase in number of Fos-activated cells. These results demonstrate for the first time that ghrelin agonists, regardless of their different chemical nature, have a significant and similar activating impact on specific groups of neurons that can be a part of the circuits involved in the food intake regulation. Therefore there is a real potency for ghrelin agonists to treat cachexia and food intake disorders. Thus, likewise JMV1843, the other ghrelin agonists represent substances that might be involved in trials for clinical purposes