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G Leng

Publications and source records attributed to G Leng.

At least 55 records · Page 3Linked to original sources
PubMed1999

Physiological pathways regulating the activity of magnocellular neurosecretory cells.

Magnocellular oxytocin and vasopressin cells are among the most extensively studied neurons in the brain; their large size and high synthetic capacity, their discrete, homogeneous distribution and the anatomical separation of their terminals from their cell bodies, and the ability to determine their neuronal output readily by measurements of hormone concentration in the plasma, combine to make these systems amenable to a wide range of fundamental investigations. While vasopressin cells have intrinsic burst-generating properties, oxytocin cells are organized within local pattern-generating networks. In this review we consider the rôle played by particular afferent pathways in the regulation of the activity of oxytocin and vasopressin cells. For both cell types, the effects of changes in the activity of synaptic input can be complex.

Afferent Pathways↗
PubMed1999

An electrophysiological and morphological investigation of the projections of growth hormone-releasing peptide-6-responsive neurons in the rat arcuate nucleus to the median eminence and to the paraventricular nucleus.

Growth hormone-releasing peptide-6 injection induces c-fos messenger RNA expression in many arcuate nucleus neurons, and sub-populations of neurons in this region project to the hypothalamic paraventricular nucleus. We examined electrophysiologically whether arcuate nucleus neurons that project to the paraventricular nucleus also project to the median eminence, and whether these neurons are activated by systemic injection of growth hormone-releasing peptide-6. Of 116 arcuate nucleus neurons tested, 43 were antidromically-identified as projecting to the paraventricular nucleus and a further 30 as projecting to the median eminence; these populations displayed distinct electrophysiological characteristics, and contrasting patterns of orthodromic response to stimulation of the median eminence and paraventricular nucleus, indicating that these two populations are functionally distinct with limited communication between them. Only one cell was antidromically-identified as projecting to both these regions. Three of 10 arcuate nucleus neurons that projected to the paraventricular nucleus were activated by injection of growth hormone-releasing peptide-6. In parallel experiments, we examined whether Fos protein expression is induced in arcuate nucleus neurons that project to the paraventricular nucleus, as identified by retrograde-labelling with FluoroGold. Immunocytochemical studies revealed that 20% of arcuate nucleus neurons that were retrogradely-labelled from the paraventricular nucleus were Fos-positive following growth hormone-releasing peptide-6 injection, although cells that were both Fos-positive and retrogradely-labelled accounted for less than 5% of the total number of Fos-positive arcuate nucleus neurons. These results confirm that there is a direct projection from the arcuate nucleus to the paraventricular nucleus and indicate that growth hormone-releasing peptide-6 activates some of these neurons.

Animals↗
PubMed1999

Kappa-opioid receptor activation inhibits post-spike depolarizing after-potentials in rat supraoptic nucleus neurones in vitro.

Endogenous agonists acting at kappa-opioid receptors modulate the discharge activity of hypothalamic supraoptic nucleus vasopressin cells in vivo. Phasic activity in vasopressin cells is known to depend critically on intrinsic mechanisms involving post-spike depolarizing after-potentials and we hypothesized that inhibition of phasic bursting by an endogenous kappa-agonist may result from reducing the magnitude of depolarizing after-potentials. To investigate this possibility, intracellular sharp electrode recordings were obtained from supraoptic nucleus cells impaled in superfused explants of rat hypothalamus. Bath application of the selective kappa-agonist, U50,488H (0.1-1 microM), decreased the spontaneous firing rate of magnocellular neurosecretory cells (by 94. 0+/-4.5% at 1 microM, mean+/-SEM; P = 0.02, n = 4). U50,488H did not alter membrane potential (0.9+/-0.8 mV hyperpolarization at 1 microM, P = 0.17, n = 8) or input resistance (11.0+/-4.5% increase at 1 microM, P = 0.09, n = 5). U50,488H (0.1 and 1 microM, both n = 5) reduced depolarizing after-potential amplitude (by 29.9+/-9.3 and 78.0+/-10. 6%, respectively, P<0.001) in eight cells in which the baseline membrane potential was kept constant by dc-current injection and in which a depolarizing after-potential was evoked every 25-40 s by a brief (40-80 ms) train of 3-6 action potentials (the number of spikes in the trains was kept constant for each cell). Thus, kappa-opioid receptor activation reduces depolarizing after-potential amplitude in supraoptic nucleus cells and this may underlie the reduction in burst duration of vasopressin cells caused by an endogenous kappa-agonist in vivo.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Role of individual susceptibility in risk assessment of pesticides.

OBJECTIVES: This study presents criteria for assessing the individual pesticide burden of workers in the chemical industry. METHODS: A group of 1003 workers exposed to methylparathion or ethylparathion (alkyl phosphates), propoxur (carbamate), or cyfluthrin (pyrethroid) was investigated. After exposure to methylparathion or ethylparathion the methylparathion or ethylparathion and methylparaoxon or ethylparaoxon concentrations in plasma, the p-nitrophenol concentration in urine, and the activities of cholinesterase and acetylcholinesterase were measured. For exposure to propoxur the propoxur concentration in plasma, the 2-isopropoxyphenol concentration in urine, and the cholinesterase and acetylcholinesterase activities were measured. For exposure to cyfluthrin the cyfluthrin concentration in plasma was measured. RESULTS: At the same propoxur concentration only workers with a low individual acetylcholinesterase activity reported symptoms. Workers who metabolised cyfluthrin rapidly reported less symptoms than workers with a lower rate of metabolism. This tendency was also evident in cases of mixed exposure (cyfluthrin and methylparathion). CONCLUSIONS: In the assessment of exposure to pesticides susceptibility of the individual person has to be considered.

Acetylcholinesterase↗
PubMed1999

Chronic central infusion of growth hormone secretagogues: effects on fos expression and peptide gene expression in the rat arcuate nucleus.

Growth hormone (GH) secretagogues induce GH release, in part, by direct actions upon anterior pituitary somatotropes and, in part, by actions upon the neuroendocrine circuitry that regulates GH secretion. In particular, acute systemic administration of GH secretagogues results in increased neuronal activity and Fos protein expression in the arcuate nucleus of the hypothalamus. Prolonged administration of GH secretagogues has been reported to have long-lasting effects upon GH release, promoting increased pulsatile secretion. Here, we investigated how chronic central infusion of GH secretagogues affects the response of arcuate nucleus neurons to acute systemic administration of GH secretagogues. In male rats, after central infusion of GH secretagogues for 5 days, there was no sustained expression of Fos in the arcuate nucleus, no significant induction of Fos expression in response to acute GH secretagogue challenge, and a greatly attenuated secretion of GH in response to acute GH secretagogue challenge, all reflecting loss of funtional responsiveness to GH secretagogues. In situ hybridisation revealed that, in the arcuate nucleus of GH secretagogue-infused rats, mRNA levels for GH-releasing hormone, neuropeptide Y and somatostatin were not different than in saline-infused animals. However, somatostatin mRNA levels in the periventricular nuclei of GH secretagogue-infused rats were significantly higher than those of saline-infused rats, indicating that this nucleus may play an important role in mediating the effects of chronic GH secretagogue administration.

Animals↗
PubMed1999

Growth hormone-releasing hormone and morphine attenuate growth hormone secretagogue-induced activation of the arcuate nucleus in the male rat.

Growth hormone secretagogues (GHS) administered systemically selectively induce growth hormone (GH) release from the pituitary and the expression of Fos protein in arcuate nucleus neurons. Both the control of GH release and the expression of the GHS receptor in the arcuate nucleus are thought to be regulated, at least in part, by the negative feedback actions of GH. In this study, we utilized the immunocytochemical detection of Fos protein to examine the effects of morphine- and GH-releasing hormone (GHRH)-induced GH release on the activation of arcuate nucleus neurons following GHS administration. Given alone, two structurally different GHS induced significant amounts of Fos-LI in the arcuate nucleus of male rats, suggesting activation of cells in this region. Prior administration of morphine or GHRH significantly reduced the number of Fos-positive cells in the arcuate nucleus of rats injected with either GHS, although when given together, morphine and GHRH did not produce a greater reduction in Fos expression than when given alone. In no case was there a complete reduction in Fos expression, indicating that some arcuate nucleus neurons are not subject to the feedback effects of endogenous GH. These results provide evidence that, in the male rat, GH can feedback to the hypothalamus, altering the responsiveness of neurons involved in the central response to GHS.

Animals↗
PubMed1998

kappa-opioid regulation of neuronal activity in the rat supraoptic nucleus in vivo.

We investigated the influence of endogenous kappa-opioids on the activity of supraoptic neurons in vivo. Administration of the kappa-antagonist nor-binaltorphimine (200 micrograms/kg, i.v.), increased the activity of phasic (vasopressin), but not continuously active (oxytocin), supraoptic neurons by increasing burst duration (by 69 +/- 24%) and decreasing the interburst interval (by 19 +/- 11%). Similarly, retrodialysis of nor-binaltorphimine onto the supraoptic nucleus increased the burst duration (119 +/- 57% increase) of vasopressin cells but did not alter the firing rate of oxytocin cells (4 +/- 8% decrease). Thus, an endogenous kappa-agonist modulates vasopressin cell activity by an action within the supraoptic nucleus. To eliminate kappa-agonist actions within the supraoptic nucleus, we infused the kappa-agonist U50,488H (2.5 micrograms/hr at 0.5 micrograms/hr) into one supraoptic nucleus over 5 d to locally downregulate kappa-receptor function. Such infusions reduced the spontaneous activity of vasopressin but not oxytocin cells and reduced the proportion of cells displaying spontaneous phasic activity from 26% in vehicle-infused nuclei to 3% in U50, 488H-infused nuclei; this treatment also prevented acute inhibition of both vasopressin and oxytocin cells by U50,488H (1000 micrograms/kg, i.v.), confirming functional kappa-receptor downregulation. In U50, 488H-infused supraoptic nuclei, vasopressin cell firing rate was increased by nor-binaltorphimine (100 and 200 micrograms/kg, i.v.) but not to beyond that found in vehicle-treated nuclei, indicating that these cells were not U50,488H-dependent. Thus, normally functioning kappa-opioid mechanisms on vasopressin cells are essential for the expression of phasic firing.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1998

Interruption of central noradrenergic pathways and morphine withdrawal excitation of oxytocin neurones in the rat.

1. We have tested the hypothesis that morphine withdrawal excitation of oxytocin neurones that follows from administration of naloxone to morphine-dependent rats is a consequence of excitation of noradrenergic neurones. 2. Female rats were made morphine dependent by intracerebroventricular (i.c.v.) infusion of the opioid at increasing doses over 5 days. On the sixth day, the rats were anaesthetized with urethane or pentobarbitone and prepared for blood sampling to determine plasma oxytocin by radioimmunoassay or for in vivo extracellular recording of the firing rate of identified oxytocin neurones from the supraoptic nucleus. Morphine withdrawal was induced by intravenous (i.v.) injection of the opioid antagonist naloxone (5 mg kg-1). 3. In one group of rats the noradrenergic projections to the hypothalamus were lesioned by i.c.v. injection of 6-hydroxydopamine immediately prior to the induction of morphine dependence. In these rats the oxytocin secretion induced by i.v. cholecystokinin was reduced to 9 % of that seen in sham-lesioned rats but in contrast, no attenuation of morphine withdrawal-induced oxytocin secretion was observed. 4. i.c.v. infusion of the alpha1-adrenoreceptor antagonist benoxathian, at up to 5.3 microg min-1, dose- dependently inhibited the withdrawal excitation of oxytocin neurones in morphine-dependent rats under urethane anaesthesia, and benoxathian reduced withdrawal-induced oxytocin secretion to 37 % of that of vehicle-infused rats. i.c.v. benoxathian also inhibited the activity of oxytocin neurones in morphine-naïve rats. Similarly, microdialysis administration of 2 mM benoxathian directly onto the surface of the supraoptic nucleus reduced the activity of oxytocin neurones by 53 %. 5. Thus noradrenergic systems are not essential for the expression of morphine withdrawal excitation, since chronic neurotoxic destruction of the noradrenergic inputs to the hypothalamus did not affect the magnitude of withdrawal-induced oxytocin secretion. However, tonically active noradrenergic inputs influence the excitability of oxytocin neurones, and acute antagonism of this noradrenergic tone can powerfully impair the ability of oxytocin neurones to exhibit morphine withdrawal excitation.

Adrenergic alpha-Antagonists↗
PubMed1998

Naloxone-induced supersensitivity of oxytocin neurones to opioid antagonists.

Here we report that a single administration of naloxone to conscious rats produces no significant increase in oxytocin release, but when repeated 3-4 days later results in a large release of oxytocin. Plasma oxytocin concentrations were measured in conscious and urethane-anaesthetized rats pretreated with naloxone or isotonic saline on Day 1. On Days 2, 3 or 4, a second dose of naloxone was given, producing an increase in oxytocin secretion in naloxone-pretreated groups (P < 0.05 vs. controls) on Day 3 and 4, but not on Day 2. The specificity of the opioid antagonist supersensitivity was determined by injection of the kappa-antagonist nor-binaltorphimine (nor-BNI). Pretreated rats (naloxone, saline or nor-BNI, Day 1) received an additional acute nor-BNI injection (Day 4) which increased plasma oxytocin concentration in the three groups. However, this increase was higher in naloxone-pretreated rats with no differences between the nor-BNI- and saline-pretreated animals. Measurements of electrical activity of single supraoptic nucleus oxytocin neurons and of plasma oxytocin concentration (Day 4) showed that naloxone modestly enhanced the responsiveness of oxytocin neurons to cholecystokinin (CCK) in naloxone-pretreated rats (by comparison with saline-pretreated rats), but had only a small effect on basal firing rate that did not differ between naloxone-pretreated rats and saline-pretreated rats. To investigate whether naloxone-pretreatment modified the effect of morphine on CCK-induced oxytocin release, on Day 4 CCK was injected i.v. with or without morphine. Morphine at a dose of 0.1 mg/kg did not affect CCK-induced oxytocin release, whereas 1 mg/kg of morphine blocked this release in both saline- and naloxone-pretreated rats. The results suggest that naloxone induces opioid antagonist supersensitivity on oxytocin secretion, mainly by up-regulating kappa-opioid mechanisms on oxytocin nerve terminals in the posterior pituitary.

Animals↗