Scrotal ischemia after intravenous vasopressin therapy for hemorrhagic esophageal varices.
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Aged↗
Biomedical subjects
J T Cheng
Publications and source records attributed to J T Cheng.
Electrophysiological actions of norepinephrine in rat lateral hypothalamus. I. Norepinephrine-induced modulation of LH neuronal responsiveness to afferent synaptic inputs and putative neurotransmitters.
The present studies were conducted as part of an ongoing investigation of the effects of norepinephrine (NE) in neuronal circuits of the mammalian brain. In this report, we describe noradrenergic actions in the lateral hypothalamus (LH), an area which has been implicated in the central integration of cardiovascular regulatory mechanisms, fluid balance and ingestive behaviors. Microiontophoretically applied NE was interacted with extracellularly recorded responses of LH neurons to iontophoretically applied putative neurotransmitters gamma-aminobutyric acid (GABA), acetylcholine (ACh) and glutamate (Glu); and activation of known input pathways from the reticular thalamus (RT) and the lateral preoptic area (LPO). Peri-event histograms of cell responses were computed before, during and after NE microiontophoresis (5-50 nA) and used to quantitatively evaluate monoamine-induced effects on spontaneous and stimulus evoked activity of LH neurons. In 16 of 23 LH neurons, RT-stimulus-induced inhibition was markedly prolonged from a mean of 28.3 +/- 4.8 ms to 44.7 +/- 5.2 ms, during iontophoretic application of NE. In 22 of 38 LH cells, LPO-stimulus-induced excitatory responses were enhanced above control levels during NE administration. In further tests, inhibitory responses of LH cells to iontophoretic pulses of GABA were potentiated during NE administration in 69% (24 of 35) of the cases tested. ACh-induced excitation was potentiated in 9 of 21 cells. In 4 of these cases, otherwise subthreshold doses of ACh caused marked increases in cell firing during the period of NE administration. By contrast, Glu-evoked excitation was antagonized by NE iontophoresis in 65.5% (17 of 26) of LH cells tested. These findings indicate that, as in other noradrenergic target regions of the CNS, NE can facilitate synaptically mediated responses of LH neurons. Taken together these observations suggest that NE may play an important regulatory role in the synaptic transfer of information within LH circuits, and consequently exert considerable influence over the homeostatic functions mediated by this structure.
Acetylcholine↗
Electrophysiological actions of norepinephrine in rat lateral hypothalamus. II. An in vitro study of the effects of iontophoretically applied norepinephrine on LH neuronal responses to gamma-aminobutyric acid (GABA).
The preceding studies demonstrated that norepinephrine (NE) can consistently augment synaptically mediated (70%) and gamma-aminobutyric acid (GABA)-induced (69%) inhibitory responses of lateral hypothalamic (LH) neurons in vivo. The present experiments further characterized the interactions of NE with LH neuronal responses to GABA in terms of alpha- and beta-receptor mechanisms and demonstrated the utility of the in vitro LH tissue slice preparation as a model for future extra- and intracellular studies of NE modulatory phenomena. Extracellular activity of LH cells was recorded from diencephalic slices (450 microns) incubated in artificial cerebrospinal fluid at 33 degrees C. Interactions between iontophoretically applied NE, isoproterenol (ISO) or phenylephrine (PE) and responses of LH neurons (n = 64) to GABA microiontophoresis were quantitated and characterized using computer-generated ratemeter and histogram records. This analysis revealed two distinct actions of NE on GABA-induced responses of LH neurons. In 8 of 32 cells tested (25%), locally applied NE markedly enhanced inhibitory responses to GABA iontophoresis in a manner identical to that observed in vivo. However, in 20 cells (62.5%), iontophoretic application of NE produced a clear antagonism of GABA responses. NE also exerted dual effects on the background firing rate of LH neurons, causing both inhibition and excitation. Overall, in those cells where NE administration increased spontaneous discharge, it either antagonized or had no effect on GABA-mediated inhibition. In contrast, spontaneous firing rate was never elevated above control levels in those cases where NE potentiated GABA responses. Additional experiments demonstrated that the GABA potentiating actions of the benzodiazepine, flurazepam, were preserved in LH tissue slice preparations. In addition, iontophoretic application of the beta-agonist, ISO, routinely suppressed the spontaneous activity of LH neurons and mimicked the facilitating action of NE on GABA. Likewise, microiontophoretic application of 8-bromo cyclic adenosine monophosphate (AMP) enhanced GABA-induced inhibition of LH firing rate in each of 11 cells tested. On the other hand, local administration of the alpha agonist, PE, routinely produced NE-like antagonism of GABA inhibition along with increases in spontaneous firing rate. Taken together these findings indicate that the commonly observed in vivo phenomena of NE augmentation of GABA and suppression of LH neuron spontaneous firing can be demonstrated in vitro, and most likely result from activation of beta adrenoceptors and subsequent elevation of cyclic AMP levels.(ABSTRACT TRUNCATED AT 400 WORDS)
8-Bromo Cyclic Adenosine Monophosphate↗
Octopamine relaxes rabbit jejunal smooth muscle by selective activation of dopamine D1 receptors.
The effect of octopamine on intestinal smooth muscle of rabbit isolated jejunum has been studied. Octopamine induced a dose-dependent decrease of muscle tone and this reproducible relaxation was not modified by tetrodotoxin or by agents that acted on adrenergic nerve terminals. Adrenoceptor antagonists, at concentrations sufficient to block each adrenoceptor type, did not reduce the actions of octopamine. On the other hand, octopamine-induced relaxations were affected by agents that have the ability to change cyclic AMP (cAMP) content; such as alloxan (an adenylate cyclase inhibitor), imidazole (a stimulator of phosphodiesterase), and isobutyl methylxanthine (an inhibitor of phosphodiesterase). Direct stimulation of adenylate cyclase by octopamine was demonstrated using radioimmunoassay of cAMP. Furthermore, haloperidol and perphenazine at concentration required to block dopamine receptor sites attenuated both smooth muscle relaxation and the formation of cAMP induced by octopamine. The effect of octopamine was totally blocked by SCH 23390, an antagonist of dopamine D-1 receptors. The lack of effect of domperidone and sulpiride, antagonists of dopamine D-2 receptors, on the actions of octopamine excludes the involvement of dopamine D-2 receptors. These results suggest that octopamine acts on intestinal dopamine D-1 receptor sites to produce relaxation of rabbit jejunum through an increase of cAMP.
Adenylyl Cyclases↗
Inhibitory effect of l-ascorbic acid on the growth of astrocytes in cell culture.
The effect of l-ascorbic acid on the growth of astrocytic cells in culture was investigated. l-Ascorbic acid produced a concentration-dependent reduction of the growth of astrocytes, both in normal and tumor cells. The effect of l-ascorbic acid was similar to that of the relative acidification of the medium, except in treated concentrations greater than 10(-6) M. The effects produced by both l- and d-forms of ascorbic acid were the same. The inhibitory effect of l-ascorbic acid at greater concentrations was partially prevented by oxidized glutathione and increased by the large concentration of reduced glutathione. This result suggests that l-ascorbic acid possesses the ability to inhibit the growth of astrocytic cells in culture through the acidification of the medium at small concentrations and/or the antioxidative properties of this compound at larger concentrations.
Animals↗
New evidence for a gating action of norepinephrine in central neuronal circuits of mammalian brain.
Many previous studies have examined the effects of norepinephrine (NE) on neuronal responsiveness to synaptic inputs and putative transmitter substances and have described differential depressant actions of NE on stimulus evoked versus spontaneous discharge such that the "signal to noise" ratio of threshold responses was increased. In the present studies, similar experimental strategies employing a combination of microiontophoresis, single unit recording and afferent pathway stimulation in intact anesthetized and brain tissue slice preparations have revealed noradrenergic "gating" actions whereby weak or subthreshold synaptic stimuli can evoke threshold neuronal responses in the presence of iontophoretically applied NE or following electrical stimulation of the locus coeruleus. Overall, these results suggest that potentially threshold excitatory and inhibitory synaptic inputs may normally arrive at central neurons but appear weak or absent except during behavioral conditions favoring the synaptic release of NE. As such, these findings provide evidence that signal to noise ratio may not be the only potential modulatory action expressed by NE in noradrenergic target circuits of the mammalian brain.
8-Bromo Cyclic Adenosine Monophosphate↗
Prostaglandin E2 induced the cyclic AMP-dependent release of acetylcholine in circular muscles of the isolated guinea pig ileum.
Prostaglandin E2 (PGE2) induced a dose-dependent increase in tone of the circular muscles of guinea pig ileum in vitro. These actions of PGE2 were deleted in the cold-stored preparations and blocked by tetrodotoxin. Atropine reduced the effects of PGE2 and physostigmine potentiated the PGE2-induced contractions. The release of acetylcholine (ACh) by PGE2 was responsible for initiating this contraction. The effect of PGE2 was compared with that of an electrical stimulation which also initiated a non-receptor-mediated release of ACh. Hexamethonium abolished the effect of PGE2 but did not influence the actions of the electrical stimulations. Synaptosomal fractions of the circular muscles were prepared to study the release of [14C]ACh. However, PGE2 failed to evoke a marked increase in the efflux of radioactivity, even at the maximal concentration. Damage and/or removal of the myenteric plexus may be responsible for this result because electrical stimulations that exert a powerful spasmogenic effect on longitudinal muscles also induced an insensitive response. Alloxan and ethacrynic acid, inhibitors of adenylate cyclase, reduced the activity of PGE2 at a concentration insufficient to modify either the actions of ACh or the electrical stimulations. 3-Isobutyl-1-methylxanthine (IBMX) potentiated the responses to PGE2 at a dose sufficient to block the activity of phosphodiesterase (PDE). Imidazole, a stimulator of PDE, decreased the actions of PGE2 in a dose-dependent manner. IBMX, like imidazole, failed to modify the activities of both ACh and the electrical stimulations. These results indicate that PGE2 may function as a releaser of ACh in a cyclic AMP-dependent manner in the circular muscles of guinea pig ileum.
Acetylcholine↗
Characterization of the release of neuropeptide Y (NPY) induced by tyramine from synaptosomal preparations of rabbit jejunum.
The effect of tyramine on the secretion of neuropeptide Y-like immunoreactivity (NPY-LI) was investigated in a synaptosomal fraction prepared from rabbit jejunum. In addition to evoking the release of norepinephrine (NE), tyramine induced a dose-dependent increase of NPY-LI secretion which was insensitive to tetrodotoxin and was not affected by the removal of calcium ions from the bathing medium. Desipramine reduced the effectiveness of tyramine but did not influence the basal output of NPY-LI. There was a positive correlation between the inhibitory effect of desipramine on the NPY release and on the uptake of [14C]tyramine into synaptosomes. Guanethidine, however, at a concentration insufficient to block the uptake of tyramine reduced the release of both NE and NPY. These data suggest that tyramine enters into nerve terminals through a desipramine-sensitive mechanism, resulting in the co-release of NE and NPY which can be reduced by guanethidine.
Animals↗
Changes in central serotoninergic transmission affect clonidine analgesia in monkeys.
The effects of changes in central serotoninergic transmission on clonidine analgesia were assessed in monkeys. The minimum electrical current required for producing jaw opening is referred to as the pain threshold. Pain was induced by electrical stimulation of tooth pulp afferents. In the first series of studies, intracerebroventricular administration of clonidine (5-30 micrograms) produced dose-dependent analgesia in monkeys. The clonidine-induced analgesia was abolished or attenuated by prior injection of the animals with p-chlorophenylalanine or 5,7-dihydroxytryptamine into the third cerebral ventricle. On the other hand, pretreatment of the animals by injecting 5-HT or its precursor 5-hydroxytryptophan into the cerebral ventricle potentiated the clonidine-induced analgesia in monkeys. In the second series of experiments, administration of clonidine (1-10 micrograms) into the diencephalic periventricular gray (of the anterior hypothalamic portion), the periaqueductal gray, or the dorsal raphe nuclei also produced dose-dependent analgesia in monkeys. The analgesia induced by clonidine injection into the diencephalic periventricular gray or the periaqueductal gray was effectively antagonized by pretreatment of the animals by injecting two 5-HT receptor antagonists (such as ketanserine and methysergide) into the diencephalic periventricular gray or the periaqueductal gray. The clonidine-induced analgesia in monkeys was not affected by pretreatment of the animals with injections of either ketanserine or methysergide into the dorsal raphe nuclei. The results suggest that the functional activity of central 5-HT neurons correlate well with the analgesic sensitivity of clonidine microinjected centrally. In addition, the analgesia induced by clonidine microinjected into the diencephalic periventricular gray or the periaqueductal gray was mediated by the 5-HT receptors at the site of injection.
5,7-Dihydroxytryptamine↗
Release of neuropeptide Y (NPY) induced by tyramine in the isolated vas deferens of rat.
The effect of tyramine on the isolated vas deferens of rats was investigated. Tyramine induced a dose-dependent contraction which was blocked by phentolamine and disappeared in adrenergic denervated tissues. In the presence of an antiserum to neuropeptide Y (NPY), the contraction induced by concentrations of tyramine greater than 10 microM was markedly increased. In addition to inducing the release of 3H-norepinephrine (NE), tyramine evoked a concentration-dependent efflux of NPY-like immunoreactivity (NPY-LI) from synaptosomal preparations. This action was not modified either by the removal of calcium ion from the medium or by the pretreatment with tetrodotoxin (0.5 microM). Desipramine suppressed the NPY-LI release induced by tyramine apparently by the inhibition of the uptake of tyramine is suggested by the significant positive correlation between the reduction of 14C-tyramine uptake and the inhibition of NPY-LI release induced by desipramine (r = 0.946). Therefore, we suggest that tyramine does induce the release of NPY from rat vas deferens, in addition to effecting NE secretion.
Animals↗
Erythrocyte sodium and potassium in patients on peritoneal dialysis.
Intracellular sodium and potassium concentrations were determined on erythrocytes obtained, before and after treatment, from patients with end-stage renal disease undergoing 48-hour intermittent peritoneal dialysis. Erythrocyte sodium increased from 7.5 +/- 0.3 to 8.6 +/- 0.4 mmol/L cells with a mean of 1.1 +/- 0.1 mmol/L cells (P less than .001), but erythrocyte potassium and cellular water content were virtually unchanged. Plasma potassium decreased during dialysis from 4.2 +/- 0.2 to 3.3 +/- 0.1 mEq/L (P less than .001). The increase in red-cell sodium correlated with this decrease in plasma potassium (r = .51, P less than .01). In contrast, erythrocyte sodium and potassium in undialyzed control patients with chronic renal failure did not change over a similar period, and plasma potassium was unchanged (4.3 +/- 0.1 mEq/L before and 4.3 +/- 0.2 mEq/L after 48 hours). Incubation of postdialysis erythrocytes from the dialysis patients in their own plasma at varying potassium concentrations showed that the rise in cell sodium was blunted as the plasma potassium was increased from 3.2 +/- 0.1 to 4.5 +/- 0.2 mEq/L. These results suggest that unlike hemodialysis, which is not associated with short-term changes in red-cell electrolytes, intermittent peritoneal dialysis results in a reversible increase in erythrocyte sodium. This change appears to be causally related to the decrease in extracellular potassium concentration.
Adult↗
Participation of prostaglandin E2 in the purinergic neurotransmission of gut.
Output of prostaglandin E2 (PGE2) from guinea pig ileal strips was detected by radioimmunoassay and the effect of adenosine and adenosine nucleotides on PGE2 output investigated in vitro. Adenosine triphosphate (ATP) and alpha, beta-methylene ATP, as well as adenosine, stimulate the output of PGE2 in a concentration dependent-manner. Potency of these compounds is in the order of alpha, beta-methylene ATP greater than ATP greater than adenosine. The effect of ATP was totally blocked by the cyclooxygenase inhibitor, indomethacin. Actions of these adenylyl compounds were attenuated by apamin, an antagonist of postjunctional P2-purinoceptor-mediated activity. Effectiveness of these compounds was not modified by 8-phenyltheophylline, a P1-purinoceptor antagonist, and it was not obtained in the isolated synaptosomal preparations. In addition, effects of adenosine and adenosine nucleotides were augmented only slightly by dipyridamole, a blocker of adenosine uptake. These findings suggest that the formation of PGE2 is stimulated in muscle cells, through the postjunctional P2-purinoceptor, taking an active role in the purinergic neurotransmission of guinea pig gut.
Adenine Nucleotides↗
Clearance of ethylene glycol by kidneys and hemodialysis.
A patient with acute ethylene glycol poisoning was treated with ethanol administration and hemodialysis, and his renal function remained consistently normal. Serial measurements of serum and urine levels of urea, creatinine, ethylene glycol, and ethanol were performed to compare the relative contributions of the hemodialyzer and the patient's kidneys in clearing ethylene glycol from the blood. Simultaneous measurements of the serum-osmolal gap (corrected for ethanol) and anion gap were correlated with these data. Mean renal clearance of ethylene glycol was 27.5 +/- 4.1 ml/min, with a fractional ethylene glycol excretion of 19.8 +/- 1.5%. This was lower than the mean urea clearance of 89.4 +/- 11.0 ml/min and fractional urea excretion of 66.0 +/- 7.8%. Hemodialyzer clearance of ethylene glycol was 156 ml/min. There was a nearly exact correlation between the serum ethylene glycol level and the corrected osmolal gap (r = 0.998, p less than 0.01). The calculated renal elimination half-life of ethylene glycol was 18 hr. We conclude that with a moderate diuresis, the normal human kidney contributes significantly to the removal of ethylene glycol from the blood. Corrected serum osmolal gap provides a nearly exact approximation of the serum ethylene glycol level and is a useful therapeutic guide.
Adult↗
Picric acid-evoked release of [14C]acetylcholine from the isolated synaptosome of rat cerebral cortex.
Picric acid stimulated, in a dose-dependent manner, the release of [14C]acetylcholine (ACh) from isolated synaptosomes of rat cerebral cortex pre-loaded with labelled choline. Radioactive ACh was separated for counting from choline in the synaptosomal supernatants by a liquid cation-exchange method. Neither the nicotinic antagonist (hexamethonium) nor the muscarinic antagonists (atropine and scopolamine) affected the effectiveness of picric acid, suggesting that the action of picric acid does not occur through a cholinoceptor-mediated mechanism. Moreover, oxotremorine, but not pilocarpine, inhibited ACh release in a concentration-dependent manner in either basal- or picric acid-evoked conditions, indicating the presence of muscarinic M2-receptors for auto-regulation of ACh release. The effect of picric acid was compared with high-K+ depolarization which also initiated a non-receptor-mediated release of ACh. Deletion of calcium ion from the medium negated the effects of both drugs. The ACh-releasing effect of picric acid was totally abolished, whereas high-K+ depolarization was reduced to some extent, when tetrodotoxin was added to the medium. These results indicate that picric acid acts as a releaser of ACh in the cerebrocortex of rat.
Acetylcholine↗
Anti-inflammatory effect of saikogenin A.
Saikogenin A, an anti-inflammatory drug, is present in the crude extract of a Chinese herbal plant called Tsai-Fu. Saikogenin A was less effective in adrenalectomized rats than in normal rats in reducing the carrageenin-induced edema. Serum corticosterone and ACTH were increased in the saikogenin A-treated rats, supporting the view that stimulation of hypothalamopituitary-adrenal system is responsible for the anti-inflammatory effect of saikogenin A. This is further supported by the findings that saikogenin A did not affect the spontaneous release of corticosterone but it facilitated the ACTH-induced release. In addition, cyclic AMP in isolated pituitary and adrenal glands was increased by saikogenin A. A role for cyclic AMP as the second messenger is thus considered. Otherwise, the direct action of saikogenin A on the process of inflammation cannot be ruled out because saikogenin A also functioned in the adrenalectomized rats and it inhibited the release of histamine induced by compound 48/80. Reduction of the vascular permeability was also observed in the saikogenin A-treated rats. These results suggest that the anti-inflammatory action of saikogenin A are due to an increase in corticosterone caused by the release of ACTH and a direct effect on the process of inflammation.
Adrenocorticotropic Hormone↗
Tyramine-induced release of neuropeptide Y (NPY) in isolated rabbit intestine.
The effect of tyramine on the contractile activity of rabbit ileal segments was studied. Treatment with tyramine initiated a short-lived, fast contraction followed first by a relaxation then by a subsequent sustained contracture. Although the mechanism of the initial fast contraction remains obscure, the relaxation was abolished by the pretreatment with a combination of phentolamine and propranolol and the sustained contracture was blocked by neuropeptide Y (NPY)-antiserum. The inhibitory effect of the NPY-antiserum was produced in a dose-dependent manner. Thus, it is suggested that tyramine induced the release of NPY to initiate the subsequent sustained contracture.
Animals↗
Picric acid functions as a releaser of [14C]acetylcholine in isolated ileal synaptosomal preparations of guinea-pig.
The effect of picric acid on the release of [14C]acetylcholine has been investigated in isolated ileal synaptosomes of guinea-pig. Nicotine, high K-depolarization (50 mM KCl) and electrical field stimulation were employed to characterize the specificity of picric acid. Picric acid induced the release of labelled acetylcholine in a dose-dependent manner and this action was negated by the removal of calcium ions from the bathing medium. Tetrodotoxin (0.1 microM) abolished the actions of picric acid, nicotine or electrical field stimulation (0.1 Hz). It reduced but did not totally suppress the effect of high K-depolarization. Agents capable of affecting the content of cyclic AMP, such as forskolin and alloxan, modified the effects of picric acid or nicotine but did not influence the effects of high K-depolarization or electrical field stimulation. Indomethacin, at a concentration (1 microM) effective in inhibiting the synthesis of prostaglandins, reduced the release of acetylcholine evoked by picric acid or nicotine, but did not affect the responses to high K-depolarization or electrical field stimulation. [3H]5-hydroxytryptamine was also released by high K-depolarization at a concentration sufficient to induce the release of acetylcholine. Similar results were obtained when the frequency of electrical field stimulation was raised to 10 Hz. However, picric acid did not initiate the release of 5-hydroxytryptamine. These results suggest that picric acid functions as a releaser of acetylcholine through a mechanism different from that of other stimulants.
Acetylcholine↗
Effect of skimmianine on animal behavior.
Skimmianine, a component of Rutaceae plants, was found to have a significant inhibitory effect on spontaneous motor activity, exploratory behavior, cataleptogenic activity, conditioned avoidance response and long-term isolation-induced fighting of animals. A mild antimethamphetamine activity was also observed. Its neuroleptic activity was less potent than that of chlorpromazine.
Aggression↗