Autoradiographic mapping of cerebral blood flow responses to cholinergic stimulation of the rat substantia innominata: modulatory effect of galanin

In order to analyze the precise cerebrovascular effects of a specific cholinergic stimulation of the rat substantia innominata and their modulation by galanin, cerebral blood flow was measured by the [¹⁴C]-iodoantipyrine autoradiographic method in anesthetized (urethane and α-chloralose), artificially ventilated male Sprague–Dawley rats that received a microinjection into the substantia innominata of saline (n=7), or 63 pmol of galanin (n=8), or 50 nmoles of carbachol (n=6) or a coinjection of carbachol and galanin (n=8). Significant carbachol-induced cerebral blood flow increases were noted in ipsilateral cortices (+36%, p<0.01 in the cingulate to +82%, p<0.01 in the parietal somatosensory cortices), but also in ipsilateral hippocampus and ipsilateral thalamus. These cerebral blood flow increases were abolished by the coinjection of carbachol and galanin, while infusions of galanin alone failed to affect cerebral blood flow. Cholinergic stimulation of the substantia innominata represents thus a good model for the analysis of the detailed pharmacological properties of the cholinergic vasodilatatory basalocortical system. The existence of an inhibitory galaninergic modulation of this system could be of particular interest, in terms of cerebrovascular reactivity, in various neurodegenerative states.     

Galanin receptor antagonists decrease fat preference in Brattleboro rat.

The Brattleboro rat eats spontaneously 46% of its diet per day in fat when given a choice of carbohydrate, protein and fat. An overexpression of galanin (GAL) has been also observed in the hypothalamic paraventricular nuclei (PVN). This associative correlation has led to a hypothesis of a functional relation between central galanin expression and the preference for a lipid diet. In the present experiments, the effects of two GAL receptor antagonists, C7 and galantide, on fat consumption and central overexpression of GAL were investigated. Both antagonists were injected into either the cerebral ventricles or directly above the PVN, and the diet consumption followed for the subsequent 24h. C7 decreased significantly fat consumption when injected into the ventricles or directly above the PVN. In contrast, galantide must be injected above the PVN to show the same effect. However, the two antagonists did not modify GAL mRNA expression in the PVN when they were injected 2h before sacrifice. These experiments confirm a functional link between the preferential consumption of fat and hypothalamic Galanin; different subtypes of the GAL receptor are probably involved, since both Galanin antagonists were differently efficient in decreasing spontaneous fat selection of the Brattleboro rat.     

Galanin receptor antagonists M40 and C7 block galanin-induced feeding

Two peptide antagonists of the galanin receptor, M40 (galanin[1–13]-Pro-Pro-[Ala-Leu]₂-Ala amide) and C7 (galanin[1–13]-spantide amide), significantly inhibited galanin-induced consumption of a palatable wet cookie mash, when microinjected intraventricularly to satiated rats. Antagonists were effective at doses equimolar to or less than the active doses of galanin. Feeding induced by an overnight fast was not significantly different in rats microinjected with saline as compared to M40 or C7, at doses which inhibited galanin-induced feeding. The activity of the chimeric compound, C7, did not appear to be linked to the properties of its C-terminal spantide-like sequence, as C7 did not induce barrel rolling at doses which inhibited galanin-induced feeding. The IC₅₀ for displacement of¹²⁵I-[Tyr²⁶]-porcine galanin 1–29 binding in rat hypothalamic membranes was 15 nM for M40, and 0.2 nM for C7, as compared to 0.8 nM for unlabelled porcine galanin(1–29). These two structurally different galanin antagonists, both demonstrating antagonists activity in vivo in awake, behaving rats, provide promising tools for further analyses of the functional activity of galanin in the mammalian brain.     

Galanin-containing neurons in the solitary nucleus and locus coeruleus of spontaneously hypertensive rats are associated with genetic hypertension

Spontaneously hypertensive (SHR) rats contained more galanin (GAL) content and GAL mRNA in locus coeruleus (LC) at the prehypertensive, but not at the well-established hypertensive stage, than did age-matched Wistar-Kyoto (WKY) rats. However, there was also more GAL content, but not GAL mRNA, in the nucleus tractus solitarii (NTS) of SHR rats than WKY rats at both stages. This study suggests that galaninergic neurons in the LC and NTS may participate in the pathogenesis of genetic hypertension.     

Intrathecal galanin at low doses increases spinal reflex excitability in rats more to thermal than mechanical stimuli

Summary The neuropeptide galanin (GAL) was injected intrathecally (i.t.) in decerebrate, spinalized, unanesthetized rats and its effect on the nocifensive flexor reflex was examined. The reflex, which was evoked by intense mechanical or thermal stimulation of the foot, was recorded from the ipsilateral hamstring muscles. I.t. GAL increased reflex excitability significantly more to thermal than to mechanical stimuli. It is suggested that GAL, which is present in sensory fibers that innervate the skin, is released by the central terminals of cutaneous afferents that are much more sensitive to thermal than to mechanical stimuli.     

大鼠实验性牙移动过程中三叉神经节内甘丙肽表达的研究

目的：研究实验性牙移动过程中大鼠三叉神经节内甘丙肽表达的变化,探讨其与正畸疼痛缓解之间是否具有内在的联系。方法：选择雄性Wistar大鼠35只,建立正畸牙移动动物模型,将大鼠随机分为实验组与空白对照组。实验组左侧为加力侧,右侧为未加力侧,左右自身对照,分别于加力6h、12h、1、3、5、7d后处死动物,取大鼠三叉神经节,标本制备,进行免疫组织化学染色与图像分析。采用SPSSl6．0统计学软件进行统计学分析。结果：与空白对照组相比,实验组加力1d甘丙肽阳性细胞数增多,表达增强（P〈O．05）;加力3d阳性细胞数增多明显（P〈O．01）;加力5d甘丙肽免疫阳性细胞数达到高峰,神经节细胞中甘丙肽免疫阳性染色呈强阳性表达（P〈0．01）。实验组未加力侧各时间点与空白对照组之间甘丙肽表达无统计学差异。结论：GAL作为内源性镇痛物质与正畸牙移动所致牙体与牙周疼痛的缓解具有一定的内在联系。     

飞行因素对人体血浆甘丙素的影响及其意义

观察飞行因素对人体血浆甘丙素（ｇａｌａｎｉｎ,ＧＡＬ）的影响及其与内皮素（ｅｎｄｏｔｈｅｌｉｎ,ＥＴ）和血管活性肠肽（ｖａｓｏａｃｔｉｖｅ ｉｎｔｅｓｉｎａｌ ｐｅｐｔｉｄｅ,ＶＩＰ）的关系。方法：对１６名飞行员进行研究,观察特技飞行前的血浆ＧＡＬ、ＥＴ和ＶＩＰ的变化。结果：（１）飞行后２０ｍｉｎ,血浆ＧＡＬ较飞行前明显升高（Ｐ〈０．０１）,至飞行后６ｈ,仍未恢复至飞行前水平（Ｐ〈０．０５）。（２