Secretin attenuates the hereditary repetitive hyperactive movements in a mouse model

It was previously demonstrated that secretin influenced the behavior of rats investigated by open-field test. In the present experiment, we have compared the effect of intracerebroventricular administration of 2 mug of secretin on the behavior of CFLP white and Japanese waltzing mice. These latter animals exhibit stereotypic circular movements. The effect of secretin on the horizontal (ambulation) and vertical movements (rearing and jumping) was investigated in open-field test. The ambulation time and distance were shorter, and the number of rearing and jumping were much lower in Japanese waltzing mice than in CFLP white mice during 30 min-experimental period. In white mice, 2 mug of secretin had no effect on the above-mentioned parameters; however, in Japanese waltzing mice, secretin enhanced the ambulation time and distance to the level of CFLP white mice, but did not influence the rearing and jumping. On the basis of the results, it was concluded that intracerebroventricularly administered secretin attenuated the stereotypic (circulating) movement and improved the horizontal movement indicated by the normalization of the ambulation time and distance; however, it did not influence the explorative behavior (rearing and jumping) in our special animal model

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

PACAP was discovered 30 years ago in Dr. Akira Arimura's laboratory. In the past three decades since then, it has become evident that this peptide plays numerous crucial roles in mammalian organisms. The most important functions of PACAP are the following: 1. neurotransmitter, 2. neuromodulator, 3. hypophysiotropic hormone, 4. neuroprotector. This paper reviews the accumulated data regarding the distribution of PACAP and its receptors in the mammalian hypothalamus and pituitary gland, the role of PACAP in the gonadotropin hormone secretion of females and males. The review also summarizes the interaction between PACAP, GnRH, and sex steroids as well as hypothalamic peptides including kisspeptin. The possible role of PACAP in reproductive functions through the biological clock is also discussed. Finally, the significance of PACAP in the hypothalamo-hypophysial system is considered and the facts missing, that would help better understand the function of PACAP in this system, are also highlighted

Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

BACKGROUND AND PURPOSE: Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. METHODS: Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. RESULTS: VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5'-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. CONCLUSIONS: VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD

Az adenilát-cikláz-aktiváló polipeptid (PACAP) klinikai jelentősége = Clinical importance of adenylate cyclase-activating polypeptide (PACAP)

A hypophysis adenilát-cikláz-aktiváló polipeptidet (PACAP) birkahypothalamusból izolálták és karakterizálták. Leírták aminosav-szekvenciáját, génjét, receptorait, azok génjét és a szervezetben történő előfordulását. A PACAP a szekretin peptidcsalád tagja. Legközelebbi rokona a vazoaktív intestinalis polipeptid (VIP). Széles körű előfordulása arra utal, hogy a peptidcsalád más tagjaihoz hasonlóan jelentős szerepet játszik élettani folyamatokban. Állatmodelleken végzett kísérletek segítségével világszerte intenzíven kutatják a PACAP szerepét különböző betegségek lehetséges kezelésében. Az összefoglaló munka első része tartalmazza a legfontosabb kísérleti adatokat a peptid és receptorának szerkezetére, génjére és emlősszervezetben történő előfordulására vonatkozóan. A második részben elsősorban a humán anyagon végzett legfontosabb vizsgálatokat tekintettük át szervrendszerek szerint. Azokat az eredményeket gyűjtöttük össze, amelyek alapján a jövőben esély lehet arra, hogy a PACAP terápiás célra használható legyen. A későbbiekben felmerül annak lehetősége, hogy a PACAP vérben mért koncentrációjának meghatározása a klinikai diagnózis, a differenciáldiagnózis felállításában segítséget nyújthat. A jövőben lehetőség nyílhat PACAP-receptort kifejező daganatok nem invazív terápiájára. A PACAP részt vesz a hypophysis elülső lebenye működésének, a vazopresszin-kidobásnak, az adrenalinszekréciónak, az inzulinszekréciónak a szabályozásában, simaizom-relaxáns, immunszuppresszor. Az idegrendszerben neurotranszmitter, neuroprotektív agyi ischaemiában, Parkinson-kórban, Huntington-choreában, Alzheimer-betegségben és a központi idegrendszer traumás sérülése esetén. A PACAP gátolja az apoptózist, védő hatású oxidatív stresszben, gátolja a proinflammatiós, de serkenti az antiinflammatiós faktorok képződését. A PACAP stimulálja a daganatos sejtek fejlődését, és citoprotektív a perifériás szervekben is. Részt vesz az élettani működések napi ritmusának szabályozásában. | The pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and characterized from sheep hypothalami. Its amino acid sequence, gene, receptors and receptor genes and its distribution in the mammalian organism were soon described. PACAP is a member of the secretin peptide family. Its closest relative is the vasoactive intestinal polypeptide (VIP). Its widespread occurrence suggests that it plays a significant role in physiological processes. With the aim of animal models, the role of PACAP was intensively investigated worldwide in a possible treatment of various diseases. The first part of this work contains the most important experimental data regarding the structure, genes and occurrence of the peptide and its receptors in mammalian body. In the second part, we overviewed the ever-increasing data on human material according to organ systems. The review contains the data where there is a chance to use PACAP for therapeutic purposes in the clinical practice. Determining the concentration of PACAP in the blood would help in establishing a clinical and differential diagnosis. In the future, there may be a possibility for non-invasive therapy of tumors expressing PACAP receptors. PACAP regulates the pituitary functions, stimulates vasopressin release, adrenalin secretion, insulin secretion. It is smooth muscle relaxant, immunosuppressant. PACAP is a neurotransmitter, it is neuroprotective in various diseases of the nervous system and cytoprotective in peripheral organs. PACAP inhibits apoptosis and the formation of pro-inflammatory factors and stimulates the anti-inflammatory factors and development of tumor cells. PACAP participates in regulating the daily rhythm of physiological functions

Intranasal Application of PACAP and β-Cyclodextrin Before the “Critical Period of Proestrous Stage” Can Block Ovulation

Introduction: It was previously shown that intracerebroventricular administration of pituitary adenylate cyclase-activating polypeptide (PACAP) prior to GnRH mobilization in proestrus prevents ovulation in rats. In this study, we examined whether PACAP given intranasally could influence luteinizing hormone (LH) and prolactin (PRL) surges and ovulation. Methods: On the day of proestrus PACAP, β-cyclodextrin (modifier of blood–brain barrier) or PACAP + β-cyclodextrin was applied intranasally between 12:30 and 13:00. Blood samples were taken at 16:00, 18:00, and 20:00 for measuring plasma hormone levels. In the next morning, the expelled ova were counted. β-cyclodextrin was also administered to male and diestrous female rats between 12:30 and 13:00 and blood was taken at 18:00. Results: PACAP prevented LH and PRL surges and ovulation in about half of the rats, β-cyclodextrin alone more effectively prevented ovulation. When PACAP and β-cyclodextrin were administered together, more rats ovulated like when PACAP given alone. β-cyclodextrin did not influence LH and PRL levels in diestrous females; however, in males, it significantly enhanced PRL level. Discussion: Not only the intracerebroventricular, but the intranasal application of PACAP prevented ovulation. β-cyclodextrin alone is more effective than PACAP and enhances PRL levels in male rats. PACAP and β-cyclodextrin given together weaken each other’s effect. β-cyclodextrin, as excipient of various drugs, has to be used carefully in human medications

Distribution of PACAP and its mRNA in several nonneural tissues of rats demonstrated by sandwich enzyme immunoassay and RT-PCR technique

The presence of PACAP in various organs was previously demonstrated using immunohistochemistry and radioimmunoassay. The aim of our work was to get information whether the presence of immunoreactive PACAP in various organs, mainly in the gastric mucosa, also indicates the place of its synthesis. The immunoreactive PACAP and its mRNA were measured in parallel assays using sandwich enzyme immunoassay (S-EIA) and RT-PCR technique. PACAP and its mRNA were demonstrated in the pancreas, testes, adrenal glands, ovaries, and in the oxyntic mucosa of the stomach. These results support our previous observation that PACAP is present not only in the nervous system and endocrine glands, but might be synthetized in the oxyntic mucosa of the stomach as well

Cell immunoblot assay study demonstrating the release of PACAP from individual anterior pituitary cells of rats and the effect of PACAP on LH release.

The presence of pituitary adenylate cyclase activating polypeptide (PACAP) was previously demonstrated in the anterior pituitary by radioimmunoassay, immunohistochemistry, and reverse transcript-polymerase chain reaction (RT-PCR). With the use of cell immunoblot assay (CIBA), when the pituitary cells were cultured on nitrocellulose membrane, the release of PACAP by individual anterior pituitary cells was observed. The released peptide, trapped by the nitrocellulose membrane forming a blot around the cells, was demonstrated by immunocytochemistry. Double labeling revealed that a part of PACAP-immunoreactive cells can release LH as well. With the use of sandwich enzyme immunoassay (S-EIA), it was found that the concentration of PACAP in the anterior pituitaries is 10(-10) M. In cell culture in a similar concentration, PACAP stimulated the LH release from female gonadotropes, but did not influence it from male ones. The stimulated release of LH was indicated by the enhancement in the diameter of LH blots compared to the untreated control cultures. We concluded that PACAP may be released from the anterior pituitary cells in a concentration which would be able to influence LH release not only in vitro but under in vivo conditions as well. The effect of PACAP on LH release was different in female and male pituitary cultures