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G Leng

Publications and source records attributed to G Leng.

At least 109 records · Page 6Linked to original sources
PubMed1994

Up-regulation of nitric oxide synthase (NOS) gene expression together with NOS activity in the rat hypothalamo-hypophysial system after chronic salt loading: evidence of a neuromodulatory role of nitric oxide in arginine vasopressin and oxytocin secretion.

Chronic salt loading up-regulated the expression of neuronal nitric oxide synthase (NOS) mRNA in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus with a concomitant increase in NOS activity in the posterior pituitary. Once daily ip injection of N-omega-nitroarginine (N-Arg), a NOS inhibitor, significantly inhibited NOS activity in the posterior pituitary in a dose-dependent manner, but did not influence NOS mRNA levels. Two percent salt loading for 3 or 4 days significantly depleted the contents of both arginine vasopressin (AVP) and oxytocin (OT) in the posterior pituitary, and simultaneous treatment with daily injections of N-Arg at a dose of 10 mg/kg significantly enhanced the depletion of both AVP and OT. This effect was dose dependent and paralleled the inhibition of NOS activity in the posterior pituitary. N-Arg treatment had no effect on the levels of both AVP and OT transcripts in PVN or SON. These results suggest that NOS gene expression in the SON and PVN of the rat hypothalamus is increased during hyperosmotic stimulation and suggest a neuromodulatory role for NO in the rat hypothalamo-hypophysial system as an inhibitory regulator of AVP and OT secretion.

Amino Acid Oxidoreductases↗
PubMed1994

Induction of c-fos expression in hypothalamic magnocellular neurons requires synaptic activation and not simply increased spike activity.

Magnocellular neurons of the hypothalamic supraoptic nucleus have been shown to express the immediate-early gene c-fos in a number of experimental and physiological circumstances. In each case the induction of the immediate-early gene followed the increase in the spike activity of the cells. Since an increase in the intracellular concentration of calcium following influx through voltage-sensitive calcium channels is a known stimulus for c-fos expression and since the action potentials of these neurons have a large calcium component, we hypothesized that c-fos induction in these neurons could be attributed to calcium influx during spike activity. In the present experiments we use extracellular recording and immunocytochemistry for Fos, the protein product of c-fos, to demonstrate the activation of the cells following intracerebroventricular administration of the muscarinic agonist, carbachol. Fos expression following carbachol injection was then compared with that induced by a similar number of antidromically evoked action potentials. Antidromic activation, unlike the activation induced by carbachol, did not lead to the induction of Fos. We conclude that Fos induction in these neurons requires receptor activation rather than spike activity.

Action Potentials↗
PubMed1994

Oxytocin neurones in the supraoptic nucleus (SON) are inhibited by endogenous opioids in late pregnant rats.

Late pregnant rats exhibit endogenous opioid restraint of oxytocin cells since i.v. naloxone (NLX opioid antagonist) increases oxytocin (OXT) secretion but OXT nerve terminals become desensitised to opioids. We have studied central opioid inhibition of OXT neurones in late pregnancy by measuring SON OXT neurones firing rate, immediate early gene (Fos) expression and dendritic OXT release under the influence of NLX On day 21 of pregnancy NLX strongly potentiated cholecystokinin (CCK) excitation of OXT neurones increased Fos protein expression and increased intranuclear release of OXT in the SON; NLX was ineffective in virgin rats. The data indicate central endogenous opioid inhibition of OXT neurone activity in late pregnancy which may restrain premature OXT release.

Animals↗
PubMed1993

Growth hormone release evoked by electrical stimulation of the arcuate nucleus in anesthetized male rats.

Plasma growth hormone (GH) concentrations were measured following electrical stimulation of either the arcuate nucleus or the median eminence in urethane-anesthetized male rats. While electrical stimulation of the arcuate nucleus elicited a large pulse of GH secretion, stimulation of the median eminence was relatively ineffective. For stimulation of the arcuate nucleus, the frequency dependence of stimulus-secretion coupling for GH release was investigated by delivering 3 differing patterns of electrical stimulation, each of 2 min duration and containing 1,200 stimulus pulses: 10 Hz continuous; 20 Hz (10 s on/10 s off); and 50 Hz (2 s on/8 s off). To examine the effect of increasing the duration of the 50 Hz stimulus train on evoked GH release, a further three stimulation protocols were also tested: 50 Hz (2 s on/8 s off); 50 Hz (3 s on/7 s off) and 50 Hz (4 s on/6 s off). While evoked GH release (per stimulus pulse) was not significantly different for various frequencies of stimulation, it was greatly potentiated by increasing the duration of 50 Hz stimulus trains. These findings suggest that GH release is not linearly related to the activation of GRF neurons but is strongly facilitated with increases in burst duration.

Animals↗
PubMed1993

Effects of the selective kappa-opioid agonist U50,488 upon the electrical activity of supraoptic neurones in morphine-tolerant and morphine-naive rats.

Spontaneous electrical activity of oxytocin-secreting neurones in the rat supraoptic nucleus is depressed by the mu-opiate receptor agonist morphine, leading to a reduction in plasma oxytocin concentration. In the present experiments, the electrical activity of single neurones was recorded from the supraoptic nucleus of urethane-anaesthetized rats. For 5 days prior to the experiments the rats had received a continuous infusion of either morphine or vehicle into a lateral cerebral ventricle; this regimen of morphine treatment results in tolerance to, and dependence upon, morphine in the central mechanisms controlling oxytocin secretion. Intravenous injection of the specific kappa-opioid agonist U50,488 at low doses resulted in small but significant increases in the electrical discharge activity of some putative oxytocin neurones in both morphine-treated and morphine-naive rats. At higher doses, the kappa-agonist consistently inhibited almost all cells tested. Morphine-treated rats, despite showing tolerance to morphine itself, showed no cross-tolerance to the inhibitory actions of U50,488 upon the oxytocin system. In separate experiments both morphine and U50,488 were effective in inhibiting supraoptic neuronal activation evoked by stimulation of the region anterior and ventral to the third ventricle, and activation following systemic injection of cholecystokinin, suggesting that both opioids act upon the final common pathway--the oxytocin neurone itself.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

A pertussis toxin-sensitive G protein mediates inhibition by morphine of spontaneous electrical activity of oxytocin neurones in anaesthetized rats.

We investigated the effects of intracerebroventricular (i.c.v.) pertussis toxin upon the sensitivity of supraoptic oxytocin neurones to intravenous morphine (1-5000 micrograms/kg) in urethane-anaesthetized rats. The maximal inhibitory capacity of morphine was diminished by prior administration of pertussis toxin. Some cells were tested with both morphine and with the kappa-opioid agonist U50,488 (1-5000 micrograms/kg): U50,488-induced inhibition of firing rate was apparently unimpaired by pertussis toxin pre-treatment. The opioid inhibition of firing rate seen in the absence of and after pertussis toxin pre-treatment was naloxone-reversible. Thus a pertussis toxin-sensitive G protein may mediate the inhibitory action of morphine upon supraoptic putative oxytocin neurones or inputs to them.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons.

The synthetic hexapeptide growth hormone-releasing peptide selectively releases growth hormone in many species including man. Growth hormone-releasing peptide directly stimulates growth hormone release by an action at the level of the pituitary, at a different receptor site to that for the endogenous 44-amino acid peptide, growth hormone-releasing hormone, and when administered with growth hormone-releasing hormone has a synergistic effect. In addition to this pituitary action, we have suggested that the potent in vivo growth hormone-releasing activity of growth hormone-releasing peptide reflects a hypothalamic action and growth hormone-releasing peptide binding sites have been reported to be present in the hypothalamus. We have now found more direct evidence for a hypothalamic action of growth hormone-releasing peptide in two ways. First, we have found that a sub-population of hypothalamic neurons show strongly increased fos expression in response to systemic growth hormone-releasing peptide administration. Fos is the protein product of the immediate early gene, c-fos, which is induced in many neuronal systems following their activation. Second, extracellular recordings from putative growth hormone-releasing hormone neurons in the arcuate nucleus showed that growth hormone-releasing peptide also stimulates the firing of neurons in this area.

Animals↗
PubMed1993

Vasopressin- and oxytocin-immunoreactive hypothalamic neurones of inbred polydipsic mice.

In the late 1950s the inbred polydipsic mice, STR/N, was discovered. The early studies indicated that the extreme polydipsia was not due to a lack of vasopressin but probably due to innate thirst of unknown origin. Because the recent investigation has revealed the presence of some functional abnormality in the brain of the STR/N mouse, we now investigated, using immunohistochemical techniques, distribution of vasopressin (AVP)- and oxytocin (OXT)-containing neurones in the hypothalamus of polydipsic strain of mouse and compared with that of the control. The pattern of distribution of AVP- and OXT-immunoreactive neurones in the paraventricular (PV), supraoptic (SO), and suprachiasmatic nuclei (SCN) of the STR/N polydipsic mouse was similar to that of the control, but the number of AVP-immunoreactive neurones was more numerous in the PVN and SON and less in the SCN in the polydipsic mouse than in the control. In addition, a discrete group of AVP- and OXT-containing neurones that was not clearly seen in the control was discovered in the STR/N. These results implicate that abnormal distribution in the brain AVP and OXT contribute to the mechanism responsible for the polydipsia shown by the strain STR/N.

Animals↗
PubMed1993

The maintenance of normal parturition in the rat requires neurohypophysial oxytocin.

The neuropeptide oxytocin has long been known as a potent contractor of the uterus. However, it has remained difficult to attribute a definite role for neurohypophysial oxytocin in either the initiation or continuation of labour. Most recently, Lefebvre and colleagues have suggested that oxytocin produced in the uterus, rather than in the hypothalamus, may be more important in parturition since at term the uterus of the rat contains 70-fold more mRNA for oxytocin than the hypothalamus, and this disappears at about the time of parturition. Despite the high levels of mRNA the uterus contains only nanogram quantities of immunoreactive oxytocin per gram wet weight at term, compared to microgram quantities present in the pituitary. Here we show that activation of the neurohypophysial oxytocin system occurs, as reflected by expression of immunoreactivity for Fos in the hypothalamic supraoptic nucleus, and that this activation is indeed critical for normal parturition, since its inhibition results in a significant prolongation of parturition. In addition, we present evidence that pulsatile delivery of oxytocin into the circulation is important for the efficient progress of parturition, indicating that a major role of the neuronal circuits regulating oxytocin secretion for parturition, as is already known for suckling, is to produce an appropriately patterned hormonal output for efficient biological action.

Animals↗
PubMed1993

Endogenous opioid regulation of oxytocin secretion through pregnancy in the rat.

We have investigated the influence of endogenous opioids on oxytocin secretion during pregnancy. In blood-sampled conscious rats on days 18 and 21 of pregnancy plasma oxytocin concentration, measured by radioimmunoassay, was significantly increased compared to non-pregnant or post-partum rats. On days 15, 18 and 21 of pregnancy but not in non-pregnant, early pregnant or post-partum rats, the opioid antagonist naloxone caused a significant increase in plasma oxytocin compared to vehicle injection, indicating activation of an endogenous opioid restraint over oxytocin secretion. Electrically stimulated neural lobes isolated from 16- and 21-day pregnant rats released more oxytocin than those from non-pregnant rats. However, naloxone (10(-5) M) was less effective at potentiating, and the kappa-opioid agonist U50,488 (10(-5)M) was less effective at inhibiting, stimulated release at the end of pregnancy than in non-pregnant rats suggesting desensitization of oxytocin nerve terminals to actions of endogenous opioids. Neural lobes from male rats drinking 2% saline for 4 days also showed desensitization of oxytocin nerve endings to naloxone. Neither neural lobe content of dynorphin A(1-8), an endogenous kappa-opioid, nor prodynorphin mRNA expression, measured by in situ hybridization histochemistry in the supraoptic nucleus altered during pregnancy. However, neural lobe content of Met5-enkephalin significantly decreased by day 21 of gestation suggesting enhanced release.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Involvement of cholecystokinin receptor types in pathways controlling oxytocin secretion.

1. Intravenous administration of cholecystokinin (CCK) results in a transient activation of oxytocin neurones in the rat, and hence to oxytocin secretion: this activation is followed by expression of c-fos mRNA and of Fos-like immunoreactivity (Fos-LI) in magnocellular oxytocin neurones. Fos-like immunoreactivity is also induced in the regions of the brainstem that are thought to relay information from the periphery to the hypothalamus. 2. Administration of the selective CCKA receptor antagonist MK-329, but not the CCKB receptor antagonist L-365,260, prior to CCK injection, prevented oxytocin release as measured by radioimmunoassay and oxytocin neuronal activation as measured by electrophysiology and by the lack of induction of c-fos mRNA. 3. MK-329 abolished the release of adrenocorticotrophic hormone (ACTH) following injection of CCK. 4. MK-329 prevented the expression of Fos-LI in the hypothalamic magnocellular nuclei and in the area postrema and dorsal vagal complex of the brainstem. 5. L-365,260 had no effect on the expression of Fos-LI in the brainstem, but attenuated that seen in the hypothalamic magnocellular nuclei. 6. We conclude that CCK acts on CCKA receptors, either in the area postrema or on peripheral endings of the vagus nerve, to cause the release of hypothalamic oxytocin and ACTH. Information may be carried to the hypothalamus in part by CCK acting at CCKB receptors.

Adrenocorticotropic Hormone↗
PubMed1993

Morphine tolerance and inhibition of oxytocin secretion by kappa-opioids acting on the rat neurohypophysis.

1. The present study investigated the mechanisms by which endogenous opioids regulate oxytocin secretion at the level of the posterior pituitary gland. Effects of the selective kappa-agonist U50,488 on oxytocin secretion were studied in urethane-anaesthetized lactating rats. Oxytocin secretion in response to electrical stimulation (0.5 mA, matched biphasic 1 ms pulses, 50 Hz, 60-180 pulses) of the neurohypophysial stalk was bioassayed on-line by measuring increases in intramammary pressure, calibrated with exogenous oxytocin. Intravenous (I.V.) U50,488 inhibited electrically stimulated oxytocin secretion, without affecting mammary gland sensitivity to oxytocin. The inhibition was dose related, with an ID50 of 441 (+194, -136) micrograms/kg and was naloxone reversible. Antagonism of endogenous beta-adrenoceptor activation by propranolol (1 mg/kg) reduced the potency of U50,488. The selective mu-agonist morphine (up to 5 mg/kg), had no effect on electrically stimulated oxytocin secretion, but depressed the mammary response to oxytocin. 2. In lactating rats given intracerebroventricular (I.C.V.) morphine infusion for 5 days to induce tolerance and dependence, I.V. U50,488 still inhibited electrically stimulated oxytocin secretion, but the ID50 was reduced to 170 (+78, -54) micrograms/kg; thus at the posterior pituitary the sensitivity of kappa-receptors is enhanced rather than reduced in morphine-tolerant rats, indicating the absence of cross-tolerance. In these rats, naloxone produced a large, sustained, fluctuating increase in intramammary pressure indicating morphine-withdrawal excitation of oxytocin secretion; I.V. U50,488 diminished this response, confirmed by radioimmunoassay, demonstrating the independence of mu- and kappa-receptors regulating oxytocin secretion. 3. In pregnant rats, I.C.V. infusion of morphine from day 17-18 of pregnancy delayed the start of parturition by 4 h, but did not significantly affect the progress of parturition once established, indicating tolerance to the inhibitory actions of morphine on oxytocin secretion in parturition, and lack of cross-tolerance to endogenous opioids restraining oxytocin in parturition. 4. Neurointermediate lobes from control and I.C.V. morphine-infused virgin rats were impaled on electrodes and perifused in vitro. Vasopressin and oxytocin release from the glands was measured by radioimmunoassay. Each gland was exposed to two periods of electrical stimulation (13 Hz, for 3 min). Naloxone (5 x 10(-6) M) was added before the second stimulation; half the lobes from each I.C.V. treatment were exposed to 5 x 10(-5) M morphine throughout.(ABSTRACT TRUNCATED AT 400 WORDS)

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