Intraventricular administration of neurohypophyseal hormones interferes with the development of tolerance to ethanol

The effects of intracerebroventricularly (icv.) administered oxytocin (OXT) and lysine-8-vasopressin (LVP) on the development of hypothermic tolerance to ethanol were investigated. Mice equipped with an icv cannula were pretreated with graded doses of OXT or LVP (3 ng, 300 pg, 30 pg or 3 pg/animal) before the daily intraperitoneal ethanol (4 g/kg) injection. Two doses of OXT or LVP (3 ng or 300 pg/animal) blocked the development of hypothermic tolerance to ethanol. Smaller doses of the peptides were ineffective in inhibiting the gradual decrease in hypothermia upon repeated ethanol administration, which effect was observed in the control group. The data presented show that the central administration of these neurohypophyseal peptides blocks the development of tolerance to ethanol.     

Dorsal hippocampal dopamine receptors are involved in mediating ethanol state-dependent memory

In the present study, the effects of bilateral injections of dopaminergic agents into the hippocampal CA1 regions (intra-CA1) on ethanol (EtOH) state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-peritoneal (i.p.) administration of EtOH (0.25, 0.5 and 1 g/kg) dose dependently induced impairment of memory retention. Pre-test administration of EtOH (0.5 g/kg)-induced state-dependent retrieval of the memory acquired under pre-training EtOH (0.5 g/kg) influence. Intra-CA1 administration of the dopamine D(1) receptor agonist, SKF 38393 (0.5, 1 and 2 g/mouse) or the dopamine D(2) receptor agonist, quinpirole (0.25, 0.5 and 1 microg/mouse) alone cannot affect memory retention. While, pre-test intra-CA1 injection of SKF 38393 (2 microg/mouse, intra-CA1) or quinpirole (0.25, 0.5 and 1 microg/mouse, intra-CA1) improved pre-training EtOH (0.5 g/kg)-induced retrieval impairment. Moreover, pre-test administration of SKF 38393 (0.5, 1 and 2 microg/mouse, intra-CA1) or quinpirole (0.5 and 1 microg/mouse, intra-CA1) with an ineffective dose of EtOH (0.25 g/kg) significantly restored the retrieval and induced EtOH state-dependent memory. Furthermore, pre-training injection of the dopamine D(1) receptor antagonist, SCH 23390 (4 microg/mouse), but not the dopamine D(2) receptor antagonist, sulpiride, into the CA1 regions suppressed the learning of a single-trial passive avoidance task. Pre-test intra-CA1 injection of SCH 23390 (2 and 4 microg/mouse, intra-CA1) or sulpiride (2.5 and 5 microg/mouse, intra-CA1) 5 min before the administration of EtOH (0.5 g/kg, i.p.) dose dependently inhibited EtOH state-dependent memory. These findings implicate the involvement of a dorsal hippocampal dopaminergic mechanism in EtOH state-dependent memory and also it can be concluded that there may be a cross-state dependency between EtOH and dopamine.     

Cyclic nucleotides in the cellular action of neurohypophyseal hormones.

Cyclic 3',5'-nucleotides play an important role in the action of neurohypophyseal hormones on peripheral tissues. All available evidence indicates that cyclic AMP serves as an intracellular mediator in the regulatory action of neurohypophyseal hormones on transport of fluids and solutes across both mammalian and nonmammalian epithelial membranes. There is a close association among binding of neurohypophyseal hormones on membrane, stimulation of cyclic AMP generation, and the functional response. On the other hand, neurohypophyseal hormones have no similar effect on cyclic AMP metabolism in contractile tissues such as smooth muscle. It appears likely that neurohypophyseal hormones stimulate primarily generation of cyclic GMP in contractile tissues, and the increase in cyclic GMP levels may be associated with the contractile response. While the role of cyclic AMP in neurohypophyseal hormone effects in epithelia is firmly established, the possible role of cyclic GMP in contractile responses is largely hypothetical at the present time.     

Effects of neurohypophyseal hormones on food-reinforced classical conditioning in the rat

The effects of different doses of lysine vasopressin (LVP) and oxytocin (OXT) were studied on the six-day acquisition or extinction of a food-reinforced classical conditioning reflex (conditional stimulus: light) when intraperitoneal (ip.) injections were carried out 20 min prior to the behavioural sessions. The highest (600 mU/kg) dose of LVP inhibited acquisition, and all LVP doses tested (150, 300 and 600 mU/kg) facilitated the extinction of conditioned behaviour. These same mU doses of OXT did not significantly affect the food-reinforced conditioning, although a consequent tendency towards increased performance (the opposite action to vasopressin) was observed. When 2.5 or 25 micrograms/kg doses of desglycinamide-arginine-vasopressin (DGAVP), a 500 micrograms/kg dose of prolyl-leucyl-glycinamide (PLG) or a 1200 mU/kg dose of OXT was injected during the extinction sessions, 2.5 micrograms/kg DGAVP and 1200 mU/kg OXT significantly facilitated extinction; the other treatments were without effect. LVP in a dose of 300 or 600 mU/kg and OXT in a dose of 300, 600 or 1200 mU/kg did not influence the food intake of 22 h food-deprived rats in a nonconditional situation. The present results indicate that the effects of LVP and OXT on memory display reinforcement-dependent characteristics, and are thus indirect or non-specific in nature.     

Effect of some fragments of peptide hormones on the content of biogenic monoamines from mouse brain]

The effect of some tripeptides, which are fragments of peptide hormones, and their analogs on the content of biogenic monoamines (BM) from albino mice brain was studied. It was found that thyroliberin, melanostatin and the C-terminal tripeptide of gonadoliberin activate the dophaminergic (DA-ergic) system in the forebrain of mice treated with reserpine or haloperidol, whereas the C-terminal tripeptide of gastrin acts as a synergic blocker of the DA receptors. The N-terminal tripeptides (with and without the amido group) do not affect the content of BM. No effect of the tripeptides was observed in intact animals. It is assumed that the agonistic or antagonistic effect of the tripeptides on BM is due to certain structural peculiarities of the tripeptides, e.g. the presence of the C-terminal amido group and their endogenous nature.     

Mu-opioid receptors are involved in the tolerance to nicotine antinociception

Several studies have shown the participation of the endogenous opioid system on the antinociceptive effects and addictive properties of nicotine. The aim of the present study was to explore the involvement of the mu-opioid receptors in the development of tolerance to nicotine antinociception. Chronic treatment of C57BL/6 mice with nicotine (5 mg/kg s.c., three times daily during 12 days) resulted in tolerance to its antinociceptive responses in the tail-immersion test. We investigated the possible existence of adaptive changes in the expression and/or functional activity of mu-opioid receptors in these tolerant mice by using autoradiography of [(3)H]D-Ala(2)-MePhe(4)-Gly-ol(5) enkephalin ([(3)H]DAMGO) binding and DAMGO-stimulated guanosine [(35)S]5'-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) binding. The density of mu-opioid receptors in the spinal cord was not modified in nicotine-tolerant mice, whereas a decrease was found in the caudate-putamen, as well as in the core and the shell of the nucleus accumbens. However, the functional activity of these receptors was significantly increased in the spinal cord as a consequence of nicotine treatment. To further investigate the role of mu-opioid receptors in the tolerance to nicotine-induced antinociception, we evaluated this response in C57BL/6 mu-opioid receptor knockout mice. Chronic nicotine treatment produced tolerance in both wild-type and knockout animals, but tolerance developed faster in mice lacking mu-opioid receptors. These results indicate that mu-opioid receptors play an important role in the development of tolerance to nicotine antinociceptive effects.     

Sinorhizobium meliloti genes involved in tolerance to the antimicrobial peptide protamine

The innate resistance of plants and animals to microbial infection is mediated in part by small cationic peptides with antimicrobial activity. We assessed the susceptibility of the alfalfa symbiont Sinorhizobium meliloti to the model antimicrobial peptide protamine. Twenty-one Tn5-induced mutants showing increased sensitivity to protamine were isolated, and nine were further characterized in detail. These nine mutants carried distinct transposon insertions that affected a total of seven different genes. Three of these genes are involved in exopolysaccharide and beta-(1,2)-glucan biosynthesis (exoT, exoU and ndvB), three other genes are implicated in nitrogen metabolism, such as a putative dyhidropyrimidinase, hutU and ureF, and the last gene exhibited similarity to the ATP binding cassette family of membrane transporters. Symbiotic defects ranging from severe to moderate were displayed by some of the protamine-hypersensitive mutants suggesting that S. meliloti possess active mechanisms to counteract hypothetical cationic peptides that may be produced by its host plant.     

Phytochelatins are involved in differential arsenate tolerance in Holcus lanatus

Arsenate tolerance is conferred by suppression of the high-affinity phosphate/arsenate uptake system, which greatly reduces arsenate influx in a number of higher plant species. Despite this suppressed uptake, arsenate-tolerant plants can still accumulate high levels of As over their lifetime, suggesting that constitutive detoxification mechanisms may be required. Phytochelatins are thiol-rich peptides, whose production is induced by a range of metals and metalloids including arsenate. This study provides evidence for the role of phytochelatins in the detoxification of arsenate in arsenate-tolerant Holcus lanatus. Elevated levels of phytochelatin were measured in plants with a range of tolerance to arsenate at equivalent levels of arsenate stress, measured as inhibition of root growth. The results suggest that arsenate tolerance in H. lanatus requires both adaptive suppression of the high-affinity phosphate uptake system and constitutive phytochelatin production.     

NPR-C receptors are involved in C-type natriuretic peptide response on bile secretion

C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family. Previous studies reported the presence of natriuretic peptide receptors and mRNA CNP in the liver. In the present work, we sought to establish the role of CNP in the regulation of bile secretion in the rat and the possible pathways involved.CNP diminished basal as well as bile salt-evoked bile flow and bile acid output in a dose-dependent manner. It also reduced the excretion of sodium, chloride, and potassium but did not modify bile pH or the excretion of phospholipids, total proteins, and glutathione. Neither parasympathetic nor sympathetic blockade abolished CNP inhibitory response on bile secretion. The selective NPR-C agonist, C-ANP-(4-23) amide, diminished bile flow and the co-administration of both peptides did not further decrease it. CNP did not alter mean arterial pressure or portal venous pressure at any given doses.CNP decreased bile acid-dependent flow without affecting bile acid-independent flow. The inhibitory effect of CNP did not involve the participation of the autonomic nervous system or hemodynamic changes. The participation of NPR-C receptors in CNP response is strongly supported by present findings. The present study shows that CNP modulates bile secretion in the rat, suggesting that CNP may be part of the large family of peptides involved in the regulation of gastrointestinal physiology.     

Calcitonin gene-related peptide: Brain and spinal action on intestinal motility

The effects of intracerebroventricular (ICV) and intrathecal (IT) administration of calcitonin gene-related peptide (CGRP) on intestinal motility were examined in conscious rats chronically fitted with intraparietal electrodes in the duodeno-jejunum and a cannula in a cerebral lateral ventricle or catheter in the subarachnoid space. ICV administration of CGRP (0.5–10 μg) restores the fasted pattern of intestinal motility in fed rats in a dose-related manner. Intrathecal administration of CGRP or calcitonin also induces fasted pattern but after a 30 min delay. These effects persisted after transection of the spinal cord and no change in intestinal motility appeared after intravenous administration of CGRP at a dose effective when given IT. This study suggests that CGRP, as calcitonin, has a neuromodulatory role in the control of intestinal motility at both brain and spinal cord levels.     

Upstream kinases of plant SnRKs are involved in salt stress tolerance

Sucrose non‐fermenting 1‐related protein kinases (SnRKs) are important for plant growth and stress responses. This family has three clades: SnRK1, SnRK2 and SnRK3. Although plant SnRKs are thought to be activated by upstream kinases, the overall mechanism remains obscure. Geminivirus Rep‐Interacting Kinase (GRIK)1 and GRIK2 phosphorylate SnRK1s, which are involved in sugar/energy sensing, and the grik1‐1 grik2‐1 double mutant shows growth retardation under regular growth conditions. In this study, we established another Arabidopsis mutant line harbouring a different allele of gene GRIK1 (grik1‐2 grik2‐1) that grows similarly to the wild‐type, enabling us to evaluate the function of GRIKs under stress conditions. In the grik1‐2 grik2‐1 double mutant, phosphorylation of SnRK1.1 was reduced, but not eliminated, suggesting that the grik1‐2 mutation is a weak allele. In addition to high sensitivity to glucose, the grik1‐2 grik2‐1 mutant was sensitive to high salt, indicating that GRIKs are also involved in salinity signalling pathways. Salt Overly Sensitive (SOS)2, a member of the SnRK3 subfamily, is a critical mediator of the response to salinity. GRIK1 phosphorylated SOS2 in vitro, resulting in elevated kinase activity of SOS2. The salt tolerance of sos2 was restored to normal levels by wild‐type SOS2, but not by a mutated form of SOS2 lacking the T168 residue phosphorylated by GRIK1. Activation of SOS2 by GRIK1 was also demonstrated in a reconstituted system in yeast. Our results indicate that GRIKs phosphorylate and activate SnRK1 and other members of the SnRK3 family, and that they play important roles in multiple signalling pathways in vivo.     

Antioxidants and unsaturated fatty acids are involved in salt tolerance in peanut

To explore the possible physiological mechanism of salt tolerance in peanut, we investigated the effect of salinity on antioxidant enzyme activity, fatty acid composition, and chlorophyll fluorescence parameters. Seedlings at the initial growth stage had been treated with 0, 100, 150, 200, 250, and 300 mM NaCl for 7 days. Results showed that fresh mass and dry mass decreased with the rise of the NaCl concentration. They decreased significantly when the NaCl concentration was more than 200 mM. The PSII’s highest photochemical efficiency (F _v/F _m) was not affected before treating 250 mM NaCl. However, the PSII (ΦPSII)’s actual photochemical efficiency of decreased after treating 200 mM NaCl. Both the initial fluorescence (F _o) and non-photochemical quenching (NPQ) increased after 200 mM NaCl treatment. PSI oxidoreductive activity (ΔI/I _o) was not affected before 200 mM NaCl. The malondialdehyde (MDA) content increased with the rise of the NaCl concentration. The activities of ascorbate peroxidase (APX) and superoxide dismutase (SOD) activities increased first and then decreased, while the content of H₂O₂ and O ₂ ^?· decreased first and then increased. Treated with 150 mM NaCl, the linolenic acid (18:3) and linoleic acid (18:2) of monogalactosyldiacylglycerols (MGDG), digalactosyldiacylglycerols (DGDG), sulphoquinovosyldiacylglycerols (SQDG) as well as phosphatidylglycerols (PG), the ratio of DGDG/MGDG increased, and the opposite results were obtained with 300 mM NaCl. The double bond index (DBI) of MGDG, DGDG, SQDG, and PG also increased after treating 150 mM NaCl. These conclusions verified that increased unsaturated fatty acid content in membrane lipid of peanut leaves could improve salt tolerance by alleviating photoinhibition of PSII and PSI.