Effects of galanin on insulin and glucagon secretion in the rat

Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80 pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets was dose-dependently suppressed by galanin (10^-6-10^-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower dose levels, the peptide also inhibits basal glucagon release.     

Galanin gene expression declines with adulthood in the cholinergic fields of the horizontal diagonal band of male rats

The neuropeptide galanin (GAL) influences leaming and memory processes, perhaps by inhibiting cholinergic function. We recently reported that, in the rat, the nucleus of the horizontal limb of the diagonal band (HDB) exhibits the highest level of GAL mRNA coexpression by basal forebrain (BF) cholinergic neurons and, in the HDB, virtually all GAL mRNA-expressing neurons correspond to the cholinergic cell type. Since GAL gene expression is induced across puberty in many brain regions, we used in situ hybridization histochemistry and quantitative autoradiography to assess GAL gene expression across the rostro-caudal extent of the HDB in prepubertal and adult male rats and to determine whether GAL gene expression is also regulated during maturation in this BF region. Our results show that the number of GAL mRNA-expressing cells per section is significantly reduced in the HDB with adulthood. Post-hoc analysis indicated that these age-associated differences in the number of GAL mRNA-expressing cells per section could be ascribed to the rostral and central subregions of the HDB. Age-related differences in the labeling intensity of GAL mRNA-expressing neurons were also detected in the rostral and central subregions of the HDB. No age-associated differences in GAL gene expression were found in the caudal HDB subregion. These results suggest that: (1) in contrast to other brain regions, GAL gene expression in the cholinergic BF may be negatively regulated by factors concomitant with puberty; and (2) the inhibition of cholinergic function by cosecreted GAL may be enhanced prior to puberty within cholinergic neurons of the rostral and central aspects of the HDB.     

人血浆甘丙素的放射免疫测定及初步临床应用

人血浆甘丙素的放射免疫测定及初步临床应用１０００３７海军总医院赵云涛，石湘芸，周正谋，张昭馥，李钟孝，丁殿勋，李继达，汤健，唐朝枢，张肇康摘要应用人甘丙素及其抗血清建立了人血浆甘丙素的放射免疫测定法。其精密度、准确度、灵敏度、稳定性及特异性经验证均达...     

Human isolated small intestine: motor responses of the longitudinal muscle to field stimulation and exogenous neuropeptides

Summary (1) Longitudinal muscle strips from the human small intestine (jejunum/ileum) responded to electrical field stimulation (1–50 Hz) with frequency-related primary contractions which were largely atropine- (3 M) sensitive. When the tone was raised by addition of galanin (0.3 – 1 M), prostaglandin (PG) E₂ (1–10 M) or neurokinin A (NKA, 0.1 M), a frequency-related relaxation was evident which was potentiated by atropine. All the responses to field stimulation were abolished by tetrodotoxin (1 M), thus indicating their neural origin. (2) The atropine-sensitive primary contraction to field stimulation was virtually abolished by omega conotoxin fraction GVIA (CTX, 0.1–0.3 M) while the relaxations were CTX-resistant. The field stimulation-induced relaxations, which were observed in the presence of atropine and guanethidine (3 M), were also unaffected by apamin (0.1 M). (3) NKA and substance P (SP) produced a concentration- (1 nM–1 M for both peptides) related contraction, NKA being about 53 times more potent than SP. [Pro⁹]SP sulphone and [MePhe⁷]-NKB, selective agonists of the NK-1 and NK-3 receptor, respectively, were barely effective. On the other hand, [\Ala⁸]NKA(4–10), a selective NK-2 receptor agonist, had a potent contractile activity, similar to that of NKA. (4) Galanin (1 nM–1M) produced an atropine- and tetrodotoxin-resistant concentration-related contraction of longitudinal muscle of human isolated small intestine. The response to galanin did not show any sign of fading and was particularly suitable to study the evoked relaxations. (5) Calcitonin gene-related peptide (CGRP) (10–100 nM) consistently inhibited the nerve-mediated contractions of strips from the ileum while the effect on the jejunum was less pronounced. Vasoactive intestinal polypeptide (VIP, 0.1–1 M) inhibited nerve-mediated contractions both in the ileum and the jejunum. (6) These experiments indicate that both cholinergic excitatory and non-adrenergic non-cholinergic nerves affect motility of the longitudinal muscle of the human small intestine. Furthermore, several neuropeptides produce potent motor effects, the contractile response to tachykinins being apparently mediated by activation of NK-2 receptors.     

Autoradiographic quantitation and anatomical mapping of GTP sensitive-galanin receptors in the guinea pig central nervous system

Galanin is a 29-amino acid peptide widely distributed in the mammalian central nervous system. Galanin receptors in the guinea pig brain were visualized using [¹²⁵I]galanin by in vitro receptor quantitative autoradiography. Scatchard analysis of [¹²⁵I]galanin binding to slide-mounted sections revealed saturable binding to a single class of high affinity receptors with a K_D of approximately 1 nM. Specific [¹²⁵I]galanin binding sites were detected in a large number of brain areas (concentration range: from non detectable to 99.32 fmol/mg of tissular proteins). The anatomical mapping revealed high densities essentially in the telencephalon (e.g. lateral septal nuclei, amygdala, hippocampal dentate gyrus) and the diencephalon (e.g. the anterodorsal and medial habenular thalamic nuclei, the paraventricular, dorsomedian and median mammillary hypothalamic nuclei, the posterior lobe of the pituitary). Addition of Mg²⁺ and GTP increased binding in some areas such as the zona incerta, the median eminence and the arcuate nucleus, and decreased it in other areas such as the amygdala, the hippocampus and the mammillary nuclei. This regional heterogeneity in the effect of Mg²⁺ and GTP can be interpreted as: (1) different rates of galanin receptor occupancy by endogenous peptide; (2) a differential coupling of GTP binding proteins to galanin receptors in the brain structures; and (3) a different nature of receptors. At any rate, this study provides evidence for a specific GTP-sensitive galanin receptor in guinea pig brain with an extensive distribution suggesting various physiological implications. Comparison with studies performed in several mammals shows that the overall distribution of galanin receptors is well preserved among species. These data suggest that galanin may posses similar functional properties in the different species tested so far. Nevertheless, very distinct differences were found in some areas like the cortex, the hippocampus and the pituitary.     

Galanin receptors in the post-mortem human brain. Regional distribution of I-galanin binding sites using the method of in vitro receptor autoradiography

The distribution of putative receptors for the peptide galanin was studied in the normal post-mortem human brain by using ¹²⁵I-galanin (0.5 nM) in combination with in vitro receptor autoradiography. Specific binding of ¹²⁵I-galanin was found in a large number of brain areas throughout the neuraxis. Highest binding densities occurred in the basal forebrain and hypothalamus, while the basal ganglia, major parts of the thalamus and the tectum were found to be poor in binding sites. All cortical areas harboured ¹²⁵I-galanin binding, and in the visual cortex a laminated pattern was present. In the hippocampus, ¹²⁵I-galanin binding occurred in layer 2 of the entorhinal cortex, in the uncus and in the hippocampal-amygdala area. In the brain-stem, ¹²⁵I-galanin binding was found in serotoninergic and noradrenergic cellgroups as well as in the reticular formation and in the parabrachial nuclei. Galanin receptors may, thus, mediate the response of galanin in numerous structures in the human brain.     

甘丙素在急性心肌梗塞发病学中的意义

本文测定了３１例急性心肌梗塞（ＡＭＩ）患者血浆甘丙素（ＧＡＬ）的放免活性，结果显示ＡＭＩ患者急性期各次血浆ＧＡＬ水平明显高于对照组，伴高血压、糖尿病和心功能不全者升高更显著，ＧＡＬ与内皮素（ＥＴ）、血糖水平均呈正相关。实验性心肌梗塞大鼠血浆ＧＡＬ、血清肌酸激酶（ＣＫ）、ＣＫ同功酶（ＣＫ－ＭＢ）、丙二醛（ＭＤＡ）含量亦明显高于对照大鼠。用ＧＡＬ抗血清治疗心肌梗塞大鼠，减少坏死面积４５．４％和缩小了梗塞范围４７．１％，亦明显降低了血浆ＧＡＬ水平，抑制血清ＣＫ、ＣＫ－ＭＢ、ＭＤＡ活性，提示早期阻断ＧＡＬ的生物学效应，对防治ＡＭＩ有重要意义。     

Galanin-positive nerves of trigeminal origin innervate rat cerebral vessels

Galanin (GAL)-positive nerve fibers in rat cerebral vessels were demonstrated by immunohistochemistry, and their origin in the trigeminal ganglia and pathway in the nasociliary nerve to the vessels was shown by retrograde tracer technique and nerve transection. Some fibers in the vertebrobasilar system appear to originate in extracranial sources. With the antiserum used only few GAL fibers could be seen in the vessels, mostly in the vertebrobasilar system. In neonatally sympathectomized animals a rich network could be visualized in most pial arteries - still particularly in the vertebrobasilar system - probably as a result of a diminished competition for nerve growth factor. No vasomotor effect of GAL could be detected in isolated segments of pial arteries, neither in normal nor in sympathectomized animals, which rules out a direct postsynaptic effect on vascular tone. GAL did not display prejunctional modulatory action on the adrenergic nerves present in the vascular preparations. A sensory function of GAL is discussed.     

Interactions of galanin and morphine in the spinal antinociception in rats with mononeuropathy

The increased hind-paw withdrawal latency (HWL) to thermal stimulation and hind-paw withdrawal threshold (HWT) to mechanical stimulation induced by morphine were attenuated by intrathecal injection of 1 or 3 nmol, but not 0.3 nmol of the selective galanin antagonist galantide. The result indicated a possible interaction between galanin and opioids in the transmission of presumed nociceptive information in the spinal cord of rats with mononeuropathy.