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G Leng

Publications and source records attributed to G Leng.

At least 127 records · Page 7Linked to original sources
PubMed1993

Endogenous opioid regulation of oxytocin release during parturition is reduced in ovariectomized rats.

Pregnant rats were ovariectomized (or sham-ovariectomized) on days 17, 18 or 21 of pregnancy and oestradiol-17 beta and progesterone were replaced. Prepartum oxytocin concentrations were significantly lower in ovariectomized steroid-treated rats than in intact controls, and on day 21 of pregnancy injection of relaxin into acutely ovariectomized rats significantly increased plasma oxytocin concentrations. During parturition, injection of the opioid antagonist naloxone induced significant increases in plasma oxytocin concentration compared with saline-injected rats. The naloxone-induced increase was significantly less in ovariectomized steroid-treated rats than in rats with intact ovaries, indicating that endogenous opioid activity is less in ovariectomized rats than in intact rats. The progress of parturition in the ovariectomized steroid-treated rats was severely disrupted compared with sham-ovariectomized rats despite similar plasma oxytocin levels at the birth of pup number 2; this disruption was not overcome by injection of naloxone or by the consequent increase in oxytocin secretion, indicating deficient preparation of the uterus and birth canal in the absence of relaxin. We conclude that the decreased oxytocin concentrations prepartum, the prolongation of parturition and the decrease in opioid tone in ovariectomized steroid-treated rats may be partly due to a lack of relaxin produced by the ovary.

Animals↗
PubMed1992

c-fos may code for a common transcription factor within the hypothalamic neural circuits involved in osmoregulation.

Conscious rats were given an intraperitoneal (i.p.) injection of isotonic or hypertonic saline, and killed 10-240 min later. In the hypothalamus of hypertonic saline-injected rats, c-fos-mRNA positive cells were mainly restricted to the supraoptic and paraventricular nuclei and to structures associated with the lamina terminalis of the third ventricle, including in particular the subfornical organ, the organum vasculosum of the lamina terminalis (OVLT) and the median preoptic nucleus. These structures comprise the proposed anterior hypothalamic 'osmoreceptor complex' for regulation of vasopressin release. The time course of the appearance and disappearance of c-fos mRNA signals was similar in all regions. Thus c-fos protein (Fos) may be a common transcription factor in the hypothalamic neural circuits involved in osmoregulation.

Animals↗
PubMed1992

Naloxone potentiates the release of oxytocin induced by systemic administration of cholecystokinin without enhancing the electrical activity of supraoptic oxytocin neurones.

Studies performed in conscious female rats confirmed that iv injection of cholecystokinin octapeptide (CCK; 20 mu/kg) increased the circulating concentration of oxytocin but not that of vasopressin, and confirmed that the stimulation of oxytocin release was markedly facilitated after iv administration of naloxone (1 mg/kg), indicating attenuation of oxytocin release by endogenous opioids. To investigate the site of action of the endogenous opioids, the electrical activity of putative oxytocin neurones in the supraoptic nucleus was recorded in urethane-anaesthetised female rats. Oxytocin neurones responded to CCK injection with an increase in firing rate lasting 5-15 min, but this response was not facilitated by prior injection of naloxone. The results suggest that the opioid influence upon CCK-induced oxytocin release operates at the level of the neurosecretory terminals in the neurohypophysis rather than centrally. Since CCK does not elevate vasopressin release, it appears unlikely that dynorphin, the opioid peptide co-existing with vasopressin, is responsible in these circumstances for the cross-inhibition of oxytocin release. It is suggested that products of proenkephalin A, the met-enkephalin precursor present in the supraoptic nucleus and in the neurohypophysis itself, may be active in the regulation of oxytocin release.

Anesthesia↗
PubMed1992

The effect of morphine and naloxone administration on plasma oxytocin concentrations in the first stage of labour.

OBJECTIVE: We investigated the effect of an opiate (morphine) and an opiate antagonist (naloxone) on the maternal secretion of oxytocin in the first stage of labour. DESIGN: Patients were randomized to receive either morphine 5 mg (n = 9), naloxone 1.2 mg (n = 10) or sterile water (n = 9) which was injected intravenously. PATIENTS: Healthy women in the first stage of labour between 3 and 6 cm dilated with no prior analgesia or oxytocin administration were recruited for the study. MEASUREMENTS: Peripheral maternal oxytocin levels were measured by radioimmunoassay for 15 minutes before and 15 minutes after administration of the assigned substance. Sampling was at 2.5 minute intervals. RESULTS: Significant reduction in the mean oxytocin concentration was found in the patients who received morphine (-2.62 pmol/l/sample) but no change was found in the naloxone group (+0.57 pmol/l/sample) when compared with controls (+0.64 pmol/l/sample). CONCLUSION: Maternal oxytocin secretion is inhibited by exogenous opiates in the first stage of labour while an effect of opiate antagonism was not demonstrated.

Adult↗
PubMed1992

Mechanisms of vasopressin secretion.

The magnocellular vasopressin system of the rat has been studied intensively in recent years. This review outlines the electrophysiological characteristics of vasopressin neurons, the characteristics of stimulus-secretion coupling in the neural lobe, and describes some of the major features of the neural regulation of this system which underlie physiological regulation of vasopressin release by osmoregulatory stimuli. The major afferent pathways to the magnocellular system are now well characterised. Those involved in osmoregulation have been mapped using expression of the primary response gene c-fos as a marker for neuronal activation.

Afferent Pathways↗
PubMed1992

Relaxin increases the firing rate of supraoptic neurones and increases oxytocin secretion in the rat.

In urethane-anaesthetized ovariectomized rats, injection of porcine relaxin (7.5 and 15 micrograms/kg, i.v.) caused a sustained increase in circulating plasma oxytocin and vasopressin concentrations; 10 micrograms relaxin/rat i.v. produced a smaller but significant increase in plasma oxytocin concentration in conscious ovariectomized rats. A significant increase in oxytocin concentration and inhibition of the spontaneous milk-ejection reflex was also seen in anaesthetized (ovary intact) lactating rats following injection of relaxin (7.5 micrograms/kg, i.v.). To investigate whether relaxin acts by increasing the electrical activity of oxytocin neurones or by facilitating stimulus-secretion coupling in the pituitary, the electrical activity of neurones in the supraoptic nucleus was recorded in urethane-anaesthetized lactating rats and in ovariectomized rats. Porcine relaxin (10 micrograms/rat, i.v.) increased the firing rate of both oxytocin and vasopressin neurones in the supraoptic nucleus in lactating rats. The response to relaxin was unaffected by subsequent injection of naloxone (1 mg/kg, i.v.). Oxytocin neurones were also activated by injection of relaxin (10 micrograms/rat) into ovariectomized rats. Combining the electrophysiological data, the neuronal activation following relaxin was significantly correlated with the level of spontaneous activity prior to relaxin injection. The results show that relaxin acts centrally to increase circulating plasma oxytocin and vasopressin concentrations by an opioid-independent mechanism.

Animals↗
PubMed1991

Identification of oxytoxin cells in the rat supraoptic nucleus by their response to cholecystokinin injection.

Identification of specific cell types is fundamental to interpreting single cell recording studies. The hypothalamic supraoptic nucleus (SON) contains phasic (putative vasopressin) cells and a mixed population of continuously firing vasopressin and oxytocin cells. We injected cholecystokinin (CCK-8; i.v.), which is known to release oxytocin but not vasopressin, to see if such injections might differentiate oxytocin from vasopressin cells. Recordings made, using the ventral surgical approach to the SON in female rats under urethane anaesthesia (1.3 g/kg) from 49 non-phasic cells showed that CCK-8 (20 micrograms/kg) excited 41. Twenty of these 41 cells were tested for their response to i.v. injections of phenylephrine (10 micrograms), which interrupts the firing of putative vasopressin cells, and none were inhibited. Only one out of 8 cells recorded from suckled, lactating rats which showed a burst of spikes just before reflex milk-ejection was inhibited by phenylephrine. Injections of CCK-8 also excited 4 out of four such 'milk ejection' cells. Cells activated by CCK, cells unaffected by phenylephrine, cells activated just before reflex milk-ejection and cells which fire continuously appear to be a single population, thus continuous firing gives a good indication that an SON cell secretes oxytocin.

Animals↗
PubMed1991

Morphine actions on supraoptic oxytocin neurones in anaesthetized rats: tolerance after i.c.v. morphine infusion.

1. The effects of acute i.v. administration of morphine on putative oxytocin neurones of the supraoptic nucleus were studied in urethane-anaesthetized female rats which had been exposed to i.c.v. infusion of morphine (up to 50 micrograms h-1) or vehicle for 5 days. 2. In vehicle-infused rats, i.v. morphine inhibited the spontaneous activity of six out of seven putative oxytocin neurones. Increasing doses of morphine were given, from 1 microgram kg-1 to 5 mg kg-1. The median cumulative threshold dose to produce significant inhibition was 20 micrograms kg-1 (seven cells in six rats); six out of seven cells were inhibited at 161 micrograms kg-1. The highest doses tested inhibited by approximately 90% (excluding one unaffected cell). Inhibition was fully reversed by i.v. naloxone without overshoot, indicating a lack of acute dependence. 3. Injection of morphine i.c.v. inhibited firing at doses that were ineffective by i.v. injection and the effects of i.c.v. morphine were reversed by i.v. naloxone. 4. Acute morphine (500 micrograms kg-1 i.v.) reduced the plasma concentration of oxytocin, measured after 15 min by specific radioimmunoassay, by 34% (n = 14). 5. In lactating rats i.c.v. injection of morphine (1-2 micrograms) inhibited the activity of supraoptic neurones identified as oxytocinergic by their responses to suckling. 6. In seventeen rats infused with i.c.v. morphine the initial firing rate of twenty-eight spontaneously active, non-phasic neurones was significantly less, by 24%, than thirty-four similar cells in control rats, indicating incomplete tolerance to i.c.v. morphine. Morphine (up to 161 micrograms kg-1 given i.v.) inhibited none of nine active non-phasic neurones (P less than 0.01 compared to control rats), but at higher doses inhibited four of nine cells; the overall median threshold cumulative dose (1660 micrograms kg-1) was significantly greater than in vehicle-infused controls, indicating tolerance to i.v. morphine. In contrast with control rats, some cells (5/9) were modestly excited by low doses of morphine. Naloxone (5 mg kg-1 i.v.) produced withdrawal excitation: the firing rate of putative oxytocin neurones increased to approximately 260% of the pre-i.v. morphine value, indicating dependence in mechanisms regulating the firing rate of these neurones. 7. In morphine-infused rats, the basal firing rate of nineteen phasically active, putative vasopressin supraoptic neurones was not different in nineteen phasic cells in controls (6.4 +/- 0.7 vs. 4.2 +/- 0.6 Hz). 8. Thus morphine potently inhibits the firing of magnocellular oxytocin neurones in the female rat, inhibiting oxytocin secretion. Morphine tolerance and dependence develop during i.c.v. infusion of morphine for 5 days. Similar tolerance to and dependence upon endogenous opioids during pregnancy may be important in the preparation of oxytocin neurones for parturition.

Animals↗
PubMed1991

Electrical activation and c-fos mRNA expression in rat neurosecretory neurones after systemic administration of cholecystokinin.

1. The expression of c-fos mRNA in the rat hypothalamus was examined by in situ hybridization following systemic administration of cholecystokinin (CCK), a procedure known to activate magnocellular oxytocin neurons but not magnocellular vasopressin neurones. 2. Conscious male rats were given a single I.P. injection of 50 micrograms/kg CCK, c-fos mRNA signal was apparent in the supraoptic and paraventricular nuclei in rats killed 10 min after injection but not in uninjected or saline-(vehicle) injected rats. The density of c-fos mRNA at both sites was further elevated in rats killed 30 min or 60 min following injection, and was absent in rats killed 4 h after injection. 3. In the paraventricular nucleus the most dense expression of c-fos mRNA following CCK administration was in the medial, mainly parvocellular portion of the nucleus, in an area corresponding to the distribution of corticotrophin-releasing factor mRNA determined by in situ hybridization in adjacent sections. 4. The I.P. injection of CCK increased plasma oxytocin concentrations, measured by specific radioimmunoassay from 13 +/- 5 pg/ml in control rats to 107 +/- 9 pg/ml in the rats killed 10 min after injection, a similar response to that observed previously in urethane-anaesthetized rats. 5. In each of six urethane-anaesthetized rats, recordings were made from single neurones in the supraoptic nucleus, identified antidronomically as projecting to the posterior pituitary and identified electrophysiologically as putative oxytocin neurones. Following I.P. injection of 50 micrograms/kg CCK, the neurones increased their firing rate by a mean of 1.3 +/- 0.2 spikes/s averaged over the 10 min following injection. 6. From the appearance of c-fos mRNA in supraoptic neurones following CCK administration we conclude that this message is expressed in magnocellular oxytocin neurones, since vasopressin neuronal activity and vasopressin release is known to be unaffected by this stimulus, and since the supraoptic nucleus contains essentially only oxytocin neurones and vasopressin neurones. 7. We conclude that c-fos mRNA expression can be induced in supraoptic oxytocin neurones following brief and modest episodes of electrical activation, suggesting that c-fos may be involved in the gene regulation of these neurones under physiological conditions.

Action Potentials↗
PubMed1991

Pethidine (meperidine) inhibition of oxytocin secretion and action in parturient rats.

Pethidine (also known as meperidine and as Demerol) injected subcutaneously at 10 mg/kg into parturient rats on the birth of the second pup resulted in a marked slowing of the progress of parturition, associated with reduced plasma oxytocin concentrations. Injection of the opiate antagonist naloxone counteracted the inhibition of oxytocin secretion and largely prevented the slowing of parturition. In vitro, pethidine inhibited spontaneous, oxytocin-induced and acetylcholine-induced contractions of uteri from rats immediately post partum, and these effects were not reversed by naloxone. In anesthetized lactating rats, pethidine inhibited the suckling-induced milk-ejection reflex and attenuated oxytocin-induced contractions of mammary myoepithelium. Finally, pethidine depressed plasma oxytocin concentrations in rats given 2% saline to drink for 24 h to stimulate oxytocin secretion. Thus pethidine inhibits oxytocin secretion in all three conditions; this inhibition is probably mediated by central opioid receptors. In addition, however, pethidine depresses the oxytocin responsiveness both of mammary myoepithelium and of myometrium. The latter effect at least is not opioid mediated.

Administration, Oral↗
PubMed1990

Ablation of the region anterior and ventral to the third ventricle (AV3V region) in the rat does not abolish the release of oxytocin in response to systemic cholecystokinin.

The effect of peripheral administration of cholecystokinin octapeptide (CCK8) on release of oxytocin and vasopressin in the anaesthetized rat was investigated in sham-lesioned rats and in rats which had received electrolytic ablation of the region anterior and ventral to the third ventricle (AV3V region). CCK8 evoked a repeatable and dose-dependent release of oxytocin, but not vasopressin, into the systemic circulation of both sham and lesioned rats, confirming that in the rat CCK8 is a selective stimulus for oxytocin release, and showing that this release is not significantly impaired by lesions of the AV3V region.

Animals↗
PubMed1989

Sensitivity of magnocellular oxytocin neurones to opioid antagonists in rats treated chronically with intracerebroventricular (i.c.v.) morphine.

The identity of the subtype of opioid receptor mediating morphine dependence in relation to oxytocin neurones was investigated. Virgin female rats were implanted with a subcutaneous osmotic minipump to infuse morphine continuously (up to 50 micrograms/h) into a lateral cerebral ventricle. After 5 days of morphine infusion, rats were anesthetized with urethane, and the electrical activity of electrophysiologically identified supraoptic neurones was recorded extracellularly while opioid antagonists were injected i.v. Putative oxytocin cells were excited following low doses of naloxone HCl: 4/7 cells were excited by 1 microgram/kg, 6/7 cells by 2.5 micrograms/kg, and 11/13 cells by doses of 5-50 micrograms/kg. MR2266 ((-)-5,9 alpha-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan: an antagonist with much greater affinity for kappa-subtype opioid receptors than naloxone) excited oxytocin cells less potently: none of 9 cells was excited by 10 micrograms/kg MR2266, 2/4 cells were by 25-50 micrograms/kg, 3/9 cells by 100 micrograms/kg and only 4/8 by 200-500 micrograms/kg. At low concentrations naloxone is selective for mu-subtype opioid receptors, hence the morphine dependence of oxytocin neurones is probably via mu-receptors. Naloxone methylbromide (MRZ), a quaternary ammonium derivative of naloxone, excited oxytocin cells in morphine-treated rats, but was at least 10 times less potent than naloxone. Thus part of the morphine-withdrawal excitation of oxytocin neurones may be mediated by mu-receptors outside the blood-brain barrier.

Action Potentials↗
PubMed1989

Ablation of the region anterior and ventral to the third ventricle (AV3V region) does not impede parturition in rats.

The region anterior and ventral to the third ventricle (AV3V) region is a major source of excitatory afferents to the magnocellular neuroendocrine system, and is essential for the osmotically regulated release of oxytocin. We investigated whether this input has a similarly essential role in parturition. Rats were implanted with a guide cannula in the AV3V region on days 9-18 of pregnancy. Following the birth of the third pup, rats were anaesthetized briefly with ether and either given an electrolytic AV3V lesion or a sham procedure was carried out. In eight AV3V-lesioned rats the mean (+/- S.E.M.) median interbirth interval following the lesion was 6.3 +/- 1.2 min compared with 5.2 +/- 0.6 min in 11 sham-lesioned rats. All rats completed delivery of their litters. The mean plasma concentration of oxytocin was unchanged following the sham procedure (pre-sham 17.1 +/- 2.8 pmol/l, n = 8; 15 min post-sham 18.1 +/- 2.7 pmol/l, n = 8; 30 min post-sham 19.2 +/- 3.5 pmol/l, n = 8). In AV3V-lesioned rats, plasma oxytocin was significantly raised following the lesion (pre-lesion 14.6 +/- 1.3 pmol/l, n = 7; post-lesion 58.3 +/- 9.8 pmol/l, n = 7) and was still higher than the sham-treated group after 30 min (55.8 +/- 9.9 pmol/l). Thus there was no significant difference in the time-course of parturition between AV3V-lesioned rats and sham-lesioned rats, and no evidence that the lesion impaired the release of oxytocin. Furthermore, in rats given an AV3V lesion on the morning of the expected day of delivery, parturition was neither delayed nor disrupted, suggesting that the AV3V region does not contribute to the mechanisms controlling the onset of parturition.

Animals↗
PubMed1988

Electrophysiological evidence for a projection from the arcuate nucleus to the supraoptic nucleus.

The electrical activity of single neurones in the hypothalamic arcuate and supraoptic nuclei was recorded in urethane-anaesthetized rats. Stimulus pulses applied to the supraoptic nucleus antidromically activated 3 out of 41 cells recorded in the ipsilateral arcuate nucleus, confirming that there is a projection from the arcuate nucleus to the region of the supraoptic nucleus. Stimulation of the arcuate nucleus inhibited 17 out of 19 continuously firing (putative oxytocin) supraoptic neurones. Inhibition was followed by a marked post-stimulus excitation in 12 cells. The responses were not abolished by i.v. injection of the opioid antagonist naloxone. Thus at least part of the input to the magnocellular oxytocin system that arises from or passes through the arcuate nucleus, is not mediated by opioid peptides.

Animals↗
PubMed1988

Effects of naloxone and of intraperitoneal hypertonic saline upon oxytocin release and upon supraoptic neuronal activity.

Urethane anaesthetized male rats were given an i.p. injection of hypertonic saline to increase plasma osmotic pressure. This injection resulted in significantly elevated plasma oxytocin levels and increased discharge activity of putative oxytocin cells in the supraoptic nucleus. Subsequent injection of naloxone (1 mg/kg) i.v. resulted in a similarly large increase in plasma oxytocin, but did not affect the discharge activity of putative oxytocin neurones. The results suggest that, following an i.p. injection of hypertonic saline, endogenous opioids act at the neurosecretory terminals to partially inhibit oxytocin release.

Animals↗
PubMed1988

Haemorrhage-induced release of noradrenaline, 5-hydroxytryptamine and uric acid in the supraoptic nucleus of the rat, measured by microdialysis.

Concentrations of monoamines and metabolites and uric acid were measured in sequential 15-min microdialysis samples taken from the area of the supraoptic nucleus (SON) in 9 urethane-anaesthetized rats. A decrease in blood pressure of 40 mm Hg was induced by withdrawing 3-4 ml of blood from an indwelling jugular catheter. This decreased blood pressure was maintained for 30 min and produced a significant rise in the concentrations of noradrenaline (NA) and its metabolite 4-hydroxy-3-methoxyphenylethan-1,2-diol (MHPG) and also in 5-hydroxytryptamine (5-HT) and the purine metabolite uric acid (UA). When blood pressure was returned to normal by replacing the withdrawn blood, the concentrations of NA, MHPG, 5-HT and UA returned to pre-haemorrhage levels within 15 min. No significant changes in concentrations of dopamine and its metabolites were found, and in 7 control animals sampled 1.5-2 mm away from the SON, in the area of the olfactory tubercle, concentrations of NA, MHPG, 5-HT and UA were not significantly altered by haemorrhage-induced decreases in blood pressure.

Animals↗
PubMed1988

Neurophysiology of body fluid homeostasis.

1. Oxytocin as well as vasopressin is released in rats following systemic osmotic stimulation. There is evidence that, in the rat, oxytocin is a natriuretic hormone. 2. Osmotically-induced activation of oxytocin and vasopressin cells and osmotically-induced hormone secretion are diminished by ablation of tissue in the region anterior and ventral to the third ventricle (AV3V region). 3. The nature and identity of the osmoreceptors subserving oxytocin and vasopressin release are discussed.

Animals↗