Galaninergic System Research Articles

Modern ideas about the role of the galaninergic system in the pathogenesis of heart failure and myocardial remodeling

Despite advances in diagnosis and treatment, heart failure (HF) still remains one of the unsolved problems of modern cardiology. The appearance and progression of HF is preceded by the development of maladaptive myocardial remodeling. In this regard, the search for new molecules for therapeutic action aimed at preventing myocardial remodeling is of undoubted interest. In this context, the galaninergic system seems to be a promising target. To date, evidence has been accumulated that activation of the galaninergic system leads to an increase in cardiomyocyte protection in the early stages after myocardial injury. It has been shown that galaninergic cascades can influence myocardial remodeling, including cell death, cardiomyocyte hypertrophy, and fibrosis. Various experimental models of heart damage showed that under stress conditions and the action of galanin and its derivatives, carbohydrate metabolism in cardiomyocytes improved, oxidative stress decreased due to antioxidant effect, and hyperproduction of reactive oxygen species by mitochondria decreased. Data were also obtained that galaninergic cascades prevent cardiomycyte hypertrophy by suppressing the expression of some fetal genes. This review article describes the currently studied cellular and molecular effects of galanin on the cardiovascular system, as well as data on the role of the galaninergic system in the pathogenesis of myocardial remodeling.

Neuroanatomical characterization of the G protein-coupled receptor activity evoked by galanin-related ligands

Galanin neuropeptide is distributed throughout the mammalian nervous system modulating a plethora of diverse physiological functions, including nociception, cognition and neuroendocrine regulation. The regulation of the galaninergic system is an interesting approach for the treatment of different diseases associated to those systems. Nevertheless, the pharmacological selectivity and activities of some galanin receptor (GalR) ligands are still in discussion and seem to depend on the dose, the receptor subtype and the second messengers to which they are coupled at different brain areas. The activity of different GalR ligands on Gi/o proteins, was evaluated by the guanosine 5′-(γ-[35S]thio)triphosphate ([35S]GTPγS) autoradiography in vitro assay applied to rat brain tissue slices in the presence of galanin, M15, M35, M40, gal(2−11) or galnon. The enhancement of the [35S]GTPγS binding induced by the chimerical peptides M15, M35 and M40 was similar to that produced by Gal in those brain areas showing the highest stimulations, such as dorsal part of the olfactory nucleus and ventral subiculum. In contrast to these peptides, using gal(2−11) no effect was measured on Gi/o protein coupling in areas of the rat brain with high GalR1 density such as posterior hypothalamic nucleus and amygdala, indicating low selectivity for GalR1 receptors. The effects evoked by the non-peptide ligand, galnon, were different from those induced by galanin, behaving as agonist or antagonist depending on the brain area, but the stimulations were always blocked by M35. Thus, the activity of most used GalR ligands on Gi/o protein mediated signalling is complex and depends on the brain area. More selective and potent GalR ligands are necessary to develop new treatments aimed to modulate the galaninergic system.

The Galaninergic System: A Target for Cancer Treatment.

Simple SummaryPeptidergic systems play an important role in cancer progression. The galaninergic system (the peptide galanin and its receptors: galanin 1, 2 and 3) is involved in tumorigenesis, the invasion and migration of tumor cells and angiogenesis and it has been correlated with tumor stage/subtypes, metastasis and recurrence rate in many types of cancer. Galanin exerts a dual action in tumor cells: a proliferative or an antiproliferative effect depending on the galanin receptor involved in these mechanisms. Galanin receptors could be used in certain tumors as therapeutic targets and diagnostic markers for treatment, prognosis and surgical outcome. This review shows the importance of the galaninergic system in the development of tumors and suggests future promising clinical antitumor applications using galanin agonists or antagonists.The aim of this review is to show the involvement of the galaninergic system in neuroendocrine (phaeochromocytomas, insulinomas, neuroblastic tumors, pituitary tumors, small-cell lung cancer) and non-neuroendocrine (gastric cancer, colorectal cancer, head and neck squamous cell carcinoma, glioma) tumors. The galaninergic system is involved in tumorigenesis, invasion/migration of tumor cells and angiogenesis, and this system has been correlated with tumor size/stage/subtypes, metastasis and recurrence rate. In the galaninergic system, epigenetic mechanisms have been related with carcinogenesis and recurrence rate. Galanin (GAL) exerts both proliferative and antiproliferative actions in tumor cells. GAL receptors (GALRs) mediate different signal transduction pathways and actions, depending on the particular G protein involved and the tumor cell type. In general, the activation of GAL1R promoted an antiproliferative effect, whereas the activation of GAL2R induced antiproliferative or proliferative actions. GALRs could be used in certain tumors as therapeutic targets and diagnostic markers for treatment, prognosis and surgical outcome. The current data show the importance of the galaninergic system in the development of certain tumors and suggest future potential clinical antitumor applications using GAL agonists or antagonists.

Galanin Regulates Myocardial Mitochondrial ROS Homeostasis and Hypertrophic Remodeling Through GalR2.

The regulatory peptide galanin is broadly distributed in the central nervous systems and peripheral tissues where it modulates numerous physiological and pathological processes through binding to its three G-protein-coupled receptors, GalR1-3. However, the function and identity of the galaninergic system in the heart remain unclear. Therefore, we investigated the expression of the galanin receptors in cardiac cells and tissues and found that GalR2 is the dominant receptor subtype in adult mouse hearts, cardiomyocytes and H9C2 cardiomyoblasts. In vivo, genetic suppression of GalR2 promotes cardiac hypertrophy, fibrosis and mitochondrial oxidative stress in the heart. In vitro, GalR2 silencing by siRNA abolished the beneficial effects of galanin on cell hypertrophy and mitochondrial reactive oxygen species (ROS) production. These findings unravel new insights into the role of galaninergic system in the heart and suggest novel therapeutic strategies in heart disease.

Theoretical investigation of selective ligand binding mode of galanin receptors

The Galaninergic system consist of Galanin and its receptors, involved in neuromodulation and neurotransmission. Galanin regulate its physiologic and pathologic functions by interacting with three G-protein coupled receptors; GalR1, GalR2 and GalR3. The widespread distribution of Galanin and its receptor subtypes in central and peripheral nervous system makes them an attractive drug target for the treatment of neurological diseases. However, subtypes selective ligands paucity and little structural information related to either Galanin receptors and Galanin receptor-ligand complexes hampered the structure-based drug design. Thus computational modeling characterization strategy was utilized for Galanin receptor 3D structure prediction and subtypes ligands binding selectivity. Reported ligands with experimental activity were docked against the homology model of Galanin receptors. Further, the MD simulation and binding free energy calculation were carried out to determine the binding interactions pattern consistency and selectivity towards receptor subtype. Results of binding free energy of per residue indicate key contribution of GalR1 Phe115 and His267 in the selective binding of ligands while Tyr103, Tyr270 and His277 play major role in the selective binding of GalR3 ligands. Our study provide rationale for further in silico virtual screening of small molecules for the development of selective ligands against Galanin receptor subtypes. Communicated by Ramaswamy H. Sarma

Substance P-Immunoreactive Fiber Varicosities Appear to Innervate Galaninergic Perikarya in the Human Hypothalamus.

Introduction: Substance P (SP) is a member of the tachykinin family. In the central nervous system, SP participates among others, in the regulation of pain, learning, memory, emotion, and sexual functions. In the periphery, SP affects the gastrointestinal, cardiovascular, and urinary systems. Galanin, similarly to SP, appears to be involved in wide range of physiologic functions, including cognition, waking and sleep, feeding, mood, blood pressure, reproduction, and development, where acts as a trophic factor. The similar distribution of SP-immunoreactive (SP-IR) fibers and galanin-IR perikarya in the human hypothalamus suggests functional interaction between these neuropeptides. Methods: We have utilized double-label immunohistochemistry to reveal these putative juxtapositions. Results: The majority of galanin-IR neurons receive contacting SP-IR fibers that often cover a significant area of the galaninergic perikarya forming multiple en passant type contacts. These SP-galanin juxtapositions are located mainly in the basal part of the infundibulum/median eminence, populating the basal periventricular region as well as the basal perifornical area. Discussion: The density and the morphology of these associations suggest that these contacts are functional synapses and therefore may represent the morphological substrate of the control of SP on multiple functions regulated/modulated by galanin. SP via galanin may modulate anterior pituitary hormone secretion, as contrary to SP, high density of galanin immunoreactivity is present in the median eminence, and by innervating galanin-IR neurons projecting to other parts of the brain, SP can modulate indirectly their activities. Impact statement The present study is the first describing juxtapositions between the substance P (SP)-immunoreactive (IR) and galanin-IR neurons in the human hypothalamus. These juxtapositions may be functional synapses and they may represent the morphological substrate of the control of SP on the galaninergic system. SP via galanin may modulate anterior pituitary hormone secretion, as contrary to SP, high density of galanin immunoreactivity is present in the median eminence. Galanin, released into the hypothalamo-hypophyseal circulation, can reach the anterior pituitary and function as a hypophysiotropic substance and regulates anterior pituitary hormone secretion. SP by innervating galanin-IR neurons, which project to other parts of the brain, can modulate indirectly their activities.

Galanin receptors activation modulates myocardial metabolic and antioxidant responses to ischaemia/reperfusion stress.

The mechanisms of protective action of the neuropeptide galanin and its N-terminal fragments against myocardial ischaemia/reperfusion (I/R) injury remain obscure. The aim of this work was to study effects of a novel peptide agonist of galanin receptors [βAla14, His15]-galanin (2-15) (G1) and the full-length galanin (G2) on energy and antioxidant status of the heart with acute infarction. The peptides were synthesized by the automatic solid phase method using Fmoc technology. Their structure was identified by 1 H-NMR spectroscopy and MALDI-TOF mass spectrometry. Experiments were performed on anaesthetized open-chest rats subjected to myocardial regional ischaemia and reperfusion. Intravenous (iv) administration of optimal doses of peptides G1 and G2 (1.0 and 0.5mg/kg, respectively, at the onset of reperfusion significantly reduced infarct size (on average by 40% compared with control) and the plasma activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). These effects were associated with augmented preservation of aerobic energy metabolism, increased activity of Cu,Zn superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and decreased lipid peroxidation in the area at risk (AAR) at the end of reperfusion. Peptide G1 showed more efficient recovery of the majority of metabolic and antioxidant parameters. The results provide evidence that the galaninergic system can be considered a promising target to reduce energy dysregulation and oxidative damage in myocardial I/R injury.

Galanin decreases spontaneous resting contractions and potentiates acetyl choline-induced contractions of goldfish gut

Galanin (GAL) is a 29 amino acid peptide, first identified from the porcine intestine and widely distributed within the brain and peripheral tissues. Among GAL biological functions, its role as a potent appetite-stimulating peptide is probably the most studied. With galanin's established role in the modulation of food intake in fish, this study aims to evaluate the effects of GAL on the intestinal motility of the goldfish, Carassius auratus, using an organ bath system. Our results found that application of GAL to the organ bath causes a significant concentration-dependent decrease in the amplitude of spontaneous contractions of goldfish gut. Preincubations of intestinal strips with acetylcholine (ACh) and GAL showed that GAL increases the force of ACh-induced contractions of the goldfish gut. These results provide the first evidence for a role of GAL in gut motility in goldfish. This also suggests a crosstalk between the effects of GAL and ACh in such functions, thus pointing to a putative joint role between the two molecules. These findings offer novel information that strengthens the role of the galaninergic system in fish feeding.

Implication of galanin gene rs948854 polymorphism in depressive symptoms in adolescents

Genetic, social, and environmental conditions contribute to the development of depression, but the pathophysiological mechanisms are still unclear. Data accumulated in recent years provide significant evidence for a direct role of galanin (GAL). This study aimed to investigate the relation between SNPs in the galaninergic system and depressive symptoms in adolescents. A total of112 adolescents aged 10–18years participated in this study. The Children Depression Inventory (CDI) was used to evaluate depressive symptoms. The effects of rs948854 and rs4432027 SNPs, both located within the promoter region of the GAL gene, rs11665337 in the GALR1 receptor, and rs8836 in the GALR2 receptor on depressive symptoms were examined. The results indicated that 30.4% of the participants had depression. We found that girls were significantly more likely to be depressive than boys. Furthermore, rs948854 minor (G) allele was associated with depressive symptoms. Adolescents carrying the GG and AG genotype for the A/G (rs948854) SNP showed higher CDI scores than those carrying homozygous AA. The binomial logistic regression analysis revealed that adolescents carrying the GG genotype at SNP rs948854 had a higher likelihood of being depressive than adolescents carrying the AA or AG genotypes (P=0.033). Moreover, individuals whose mothers had a positive history for depression and who were sedentary were more likely to display depressive symptoms (P=0.013 and P=0.032, respectively). In conclusion, the SNP rs948854 in the GAL gene seems to be involved in the modulation of depressive state, especially in individuals with GG genotype.

The galanin and galanin receptor subtypes, its regulatory role in the biological and pathological functions.

The multitalented neuropeptide galanin was first discovered 30 years ago but initially no biologic activity was found. Further research studies discovered the presence of galanin in the brain and some peripheral tissues, and galanin was identified as a modulator of neurotransmission in the central and peripheral nervous system. Over the last decade there were performed very intensive studies of the neuronal actions and also of nonneuronal actions of galanin. Other galanin family peptides have been described, namely galanin, galanin-like peptide, galanin-message associated peptide and alarin. The effect of these peptides is mediated through three galanin receptors subtypes, GalR1, GalR2 and GalR3 belonging to G protein coupled receptors, and signaling via multiple transduction pathways, including inhibition of cyclic AMP/protein kinase A (GalR1, GalR3) and stimulation of phospholipase C (GalR2). This also explains why one specific molecule of galanin can be responsible for different roles in different tissues. The present review summarizes the information currently available on the relationship between the galaninergic system and known pathological states. The research of novel galanin receptor specific agonists and antagonists is also very promising for its future role in pharmacological treatment. The galaninergic system is important target for current and future biomedical research.

Combining CRISPrs with Comparative genomics; a gateway to rapidly unlocking the effects of genetic and epigenetic variation on the galaninergic system

Combining CRISPrs with Comparative genomics; a gateway to rapidly unlocking the effects of genetic and epigenetic variation on the galaninergic system

Responsiveness of pituitary to galanin throughout the reproductive cycle of male European sea bass (Dicentrarchus labrax)

The neuropeptide galanin (Gal) is a putative factor regulating puberty onset and reproduction through its actions on the pituitary. The present study investigated the pituitary responsiveness to galanin and the patterns of galanin receptors (Galrs) expression throughout the reproductive cycle of two years old male European sea bass (Dicentrarchus labrax), an important aquaculture species. Quantitative analysis of pituitary and hypothalamus transcript expression of four galr subtypes revealed differential regulation according to the testicular developmental stage, with an overall decrease in expression from the immature stage to the mid-recrudescence stage. Incubation of pituitary cells with mammalian 1–29Gal peptide induced significant changes in cAMP concentration, with sensitivities that varied according to the testicular development stages. Furthermore 1–29Gal was able to stimulate both follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) release from pituitary cell suspensions. The magnitude of the effects and effective concentrations varied according to reproductive stage, with generalized induction of Fsh and Lh release in animals sampled in January (full spermiation). The differential expression of galrs in pituitary and hypothalamus across the reproductive season, together with the differential effects of Gal on gonadotropins release in vitro strongly suggests the involvement of the galaninergic system in the regulation the hypothalamus-pituitary-gonad axis of male sea bass. This is to our knowledge the first clear evidence for the involvement of galanin in the regulation of reproduction in non-mammalian vertebrates.

The Effect of Stress on the Galaninergic System in the Rat Adenohypophysis: mRNA Expression and Immunohistochemistry of Galanin Receptors

The neuropeptide galanin is a widely distributed neurotransmitter/neuromodulator that regulates a variety of physiological processes and also participates in the regulation of stress responses. The effect of stress is dependent on the activity of the hypothalamic- adenohypophyseal-adrenal axis. Although the adenohypophysis is a crucial part of this axis, galanin peptides and their receptors have not yet been identified in this part of the pituitary after activation of the stress response. Since there are many controversies about the occurrence of individual galanin receptor subtypes in the adenohypophysis under basal conditions, we decided to verify their presence immunohistochemically, and we clearly demonstrated that the adenohypophysis expresses neuropeptides galanin, galanin-like peptide, and subtypes of galanin receptors GalR1, GalR2 and GalR3. The specificity of the reactions was confirmed by Western blots for galanin receptors. Using real-time qPCR we also demonstrated the presence of three GalR subtypes, with the highest expression of GalR2. In addition, we tested the effect of stress. We found that acute stress did not induce any changes in the GalR2 expression, but increased expression of GalR1 and decreased that of GalR3. We confirmed the involvement of the galanin system in the stress regulation in the adenohypophysis.

Effect of Stress on the Expression of Galanin Receptors in Rat Heart

Neuropeptide galanin, galanin-like peptide and galanin receptors 1, 2 and 3 are a crucial part of the so-called galaninergic system. Our previous studies have shown the possible role of this system in mood modulation, especially regarding stress. So far, the galanin receptors have been found in different tissues including brain and heart. Our study deals with changes in expression of galanin receptor subtypes in the heart of Wistar rats exposed to three different types of stress. Galanin receptor subtypes were determined in fluorescently labelled samples using specific primary antibodies, and all sections were analysed in an immunofluorescent microscope and microphotographs. Image analyses were subsequently performed by software ImageJ, using the threshold method with calculation of the DAPI/galanin receptor signal ratio. We found all three types of receptors in the right and left atria and left and right ventricles. Changes in the density of galanin receptors after application of the stressor depended on the observed heart compartment. We found a significant decrease of galanin receptor 1 in all compartments after all types of stress. For GalR2 and GalR3, the increase/decrease of density was dependent on the tested compartment. These results show that galanin receptors could be involved in the function of heart during the cardiac cycle.

Ala5-galanin (2–11) is a GAL2R specific galanin analogue

It is over 30years since the regulatory peptide galanin was discovered by Professor Mutt and co-workers. Galanin exerts its effects by binding to three galanin G-protein coupled receptors, namely GAL1R, GAL2R and GAL3R. Each galanin receptor has a different distribution in the central nervous system and the peripheral nervous system as well as distinctive signaling pathways, which implicates that the receptors are involved in different biological- and pathological effects. The delineation of the galaninergic system is however difficult due to a lack of stable, specific galanin receptor ligands. Herein, a new short GAL2R specific ligand, Ala5-galanin (2–11), is presented. The galanin (2–11) modified analogue Ala5-galanin (2–11) was tested in 125I-galanin competitive binding studies for the three galanin receptors and the G-protein coupled receptor signaling properties was tested by the ability to influence second-messenger molecules like inositol phosphate and cyclic adenosine monophosphate. In addition, two different label-free real-time assays, namely EnSpire® based on an optical biosensor and xCELLigence® based on an electric biosensor, were used for evaluating the signaling properties using cell lines with different levels of receptor expression. Ala5-galanin (2–11) was subsequently found to be a full agonist for GAL2R with more than 375-fold preference for GAL2R compared to both GAL1R and GAL3R. The single amino acid substitution of serine to alanine at position 5 in the short ligand galanin (2–11) resulted in a ligand subsequently unable to bind neither GAL3R nor GAL1R, even at concentrations as high as 0.1mM.

Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes.

There is a large body of pre-clinical and some clinical data to link the neuropeptide galanin to a range of physiological and pathological functions that include metabolism, depression, and addiction. An enhancer region upstream of the human GAL transcriptional start site has previously been characterised. In-vitro transfection studies in rat hypothalamic neurons demonstrated that the CA allele was 40% less active than the GG allele in driving galanin expression. Our hypothesis was to investigate the effect of this galanin enhancer genotype on a range of variables that relate to the known functions of the galaninergic system in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of young adults (N = 169–6,078). Initial findings showed a positive relationship of cannabis usage (OR = 2.070, P = 0.007, N = 406 (individuals who had used cannabis at least once within the last 12 months, total sample size 2731) with the GG haplotype, consistent with the previous published data linking galanin with an increased release of dopamine. As our sample size was relatively small we replicated the analysis in a larger cohort of 2,224 African Americans and 1,840 European Americans, but no discernible trend across genotypes was observed for the relationship with cannabis usage. Further, we found no association of the galanin enhancer genotype with any of the other pathophysiological parameters measured. These findings emphasise that preclinical data does not always predict clinical outcomes in cohort studies, noting that association studies are subject to multiple confounders.

Novel galanin receptors in teleost fish: Identification, expression and regulation by sex steroids

In fish, the onset of puberty, the transition from juvenile to sexually reproductive adult animals, is triggered by the activation of pituitary gonadotropin secretion and its timing is influenced by external and internal factors that include the growth/adiposity status of the animal. Kisspeptins have been implicated in the activation of puberty but peripheral signals coming from the immature gonad or associated to the metabolic/nutritional status are also thought to be involved. Therefore we hypothesize the importance of the galinergic system in the brain and testis of pre-pubertal male sea bass as a candidate to translate the signals leading to activation of testicular maturation. Here, the transcripts for four galanin receptors (GALR), named GALR1a, 1b, 2a and 2b, were isolated from European sea bass, Dicentrarchus labrax. Phylogenetic analysis confirmed the previously reported duplication of GALR1 in teleost fish, and unravelled the duplication of GALR2 in teleost fish and in some tetrapod species. Comparison with human showed that the key amino acids involved in ligand binding are present in the corresponding GALR1 and GALR2 orthologs. Transcripts for all four receptors are expressed in brain and testes of adult fish with GALR1a and GALR1b abundant in testes and hardly detected in ovaries. In order to investigate whether GALR1 dimorphic expression was dependent on steroid context we evaluated the effect of 11-ketotestosterone and 17β-estradiol treatments on the receptor expression in brain and testes of pre-pubertal males. Interestingly, steroid treatments had no effect on the expression of GALRs in the brain while in the testes, GALR1a and GALR1b were significantly up regulated by 11KT. Altogether, these results support a role for the galaninergic system, in particular the GALR1 paralog, in fish reproductive function.

Galanin modulating effect on restraint stress-induced short- and long-term behavioral changes in Wistar rats

The neuropeptide galanin has been recognized as a possible neurotransmitter/neuromodulator, and in addition has been implicated in anxiety- and depression-related behaviors. The present study demonstrates increased locomotion and rearing after galanin (0.3mg/kg) that was given intraperitoneally (i.p.) to intact Wistar rats which were tested 1h later in the open field (OF). These effects, which suggest an anxiolytic-like action, were blocked by i.p. administered peptidic galanin antagonist M40. Further, the locomotion increase caused by galanin and the inhibitory effect of M40 persisted for 48h without additional treatment. Rats exposed to restraint stress (lasting 60min) for three consecutive days and tested 1h after stress termination exhibited reduced locomotion and exploration in the OF. Galanin (0.3 and 1.0mg/kg) given immediately after each stress exposure prevented the decrease of locomotion and exploration induced by stress in all trials. When the test was repeated 6 days later without stress and galanin treatment the reduction of locomotion produced by stress persisted; the anti-stress behavioral effects of both galanin doses were also present. Testing performed on the 12th day after the last stress and galanin treatment with 0.3mg/kg revealed an increased locomotion compared with unstressed and stress-exposed rats. Our results demonstrate that behavioral effects of the peptide galanin are evident even after i.p. administration. These results also suggest that galanin elicits stress-modulatory action, and support the notion that the galaninergic system may serve as a drug target in stress-related conditions.

Inhibitory Effect of Galanin on Adrenaline- and Noradrenaline-Induced Increased Oxytocin Secretion in Rat Neurohypophyseal Cell Cultures

The effects of the interactions between the 29 amino acid-containing peptide galanin and adrenaline or noradrenaline on the secretion of oxytocin were studied in 13- to 14-day cultures of isolated rat neurohypophyseal tissue. The alpha-receptor antagonist corynanthine blocked the adrenaline-induced increase of oxytocin secretion. When the beta-receptor antagonist propranolol was added before the noradrenaline treatment, the antagonist prevented the noradrenaline-induced enhancement of oxytocin release. Following the addition of galanin, the extent of oxytocin secretion into the supernatant medium decreased. Adrenaline and noradrenaline treatments increased the oxytocin level. Preincubation with galanin reduced the adrenaline- and noradrenaline-induced oxytocin level elevations. The blocking effect of galanin was prevented by previous treatment with the galanin receptor antagonist galantid (M15). When adrenaline or noradrenaline treatment was applied before galanin addition, the oxytocin secretion remained enhanced. The present results indicate that the changes in oxytocin secretion induced by the adrenergic system can be directly influenced by the galaninergic system. The interactions between the adrenergic and galaninergic systems from the aspect of oxytocin secretion can occur at the level of the posterior pituitary, independently of the hypothalamus.

Effects of galanin–monoaminergic interactions on vasopressin secretion in rat neurohypophyseal cell cultures

The effects of dopamine (DA), serotonin (5-HT), histamine (HA), adrenaline (ADR), noradrenaline (NADR) and K + administration on vasopressin (VP) secretion were studied in 13–14-day cultures of rat neurohypophyseal (NH) cells, and it was examined whether galanin (GAL) can modify the VP release enhancement induced by these monoaminergic compounds. An enzymatic dissociation technique was used to make the rat NH cell cultures. The VP contents of the supernatants of 14-day cultures were determined by radioimmunoassay. Following the administration of 10 − 6 M GAL, the VP secretion into the supernatant media decreased. DA, 5-HT, ADR or NADR treatment increased the VP level substantially, while the enhancing effect of HA was more moderate. GAL administration before DA, ADR and NADR treatment prevented the VP concentration increase induced by DA, ADR or NADR. Preincubation with GAL reduced the 5-HT- or HA-induced VP level increases; the VP concentrations of the supernatant media remained above the control level. The GAL blocking effect was prevented by previous treatment with the GAL receptor antagonist galantid (M15). GAL had no effect on the VP level increase induced by K +, which causes a non-specific hormone secretion. The results indicate that the changes in VP secretion induced by the monoaminergic system can be directly influenced by the GAL–ergic system. The interactions between the monoaminergic and GAL–ergic systems regarding VP secretion occur at the level of the posterior pituitary.