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M Ennis

Publications and source records attributed to M Ennis.

At least 163 records · Page 9Linked to original sources
PubMed1989

Radiographic contrast media-induced histamine release: a comparative study with mast cells from different species.

Radiographic contrast media in clinical use cause unwanted allergic and pseudoallergic reactions. To investigate the mechanisms of these reactions, studies on isolated mast cells from different species and sites are necessary. In this study, the effect of six commonly used contrast media on rat (peritoneal, lung) and human (lung) mast cells was investigated. The three preparations with low osmolalities (Hexabrix, Solutrast, Ultravist) released little or no histamine from the cells examined. In contrast, the three preparations with high osmolalities (Angiographin, Telebrix, Rayvist) were potent releasing agents. However, the degree of release and the order of potency was different depending on the cells investigated. Indeed, rat peritoneal mast cells required much higher concentrations before release was observed. Since the contrast media with low osmolality also cause histamine release and reactions in vivo, other systems (e.g. complement) must be additionally involved.

Animals↗
PubMed1989

Potent inhibitory input to locus coeruleus from the nucleus prepositus hypoglossi.

Previous studies reported afferents to LC from the nucleus tractus solitarius (NTS), while more recent anatomic experiments indicate that the area of the nucleus prepositus hypoglossi (PrH), but not the NTS, provides robust innervation of LC. In the present experiments, the contribution of these two dorsomedial medullary areas to LC innervation was assessed with electrophysiologic methods in anesthetized rats. Focal electrical stimulation of LC antidromically activated a substantial number of PrH neurons; such stimulation failed to antidromically activate NTS neurons. Electrical activation of PrH evoked potent, uniform inhibition of LC discharge. In contrast, NTS activation produced only weak, long latency responses in only a few LC neurons. In agreement with these results, WGA-HRP injections into NTS did not yield consistent anterograde labeling in LC. These results confirm our previous anatomic findings that PrH, but not NTS, provides major innervation of LC. Furthermore, the input from PrH potently inhibits LC activity.

Action Potentials↗
PubMed1989

GABA-mediated inhibition of locus coeruleus from the dorsomedial rostral medulla.

Recent anatomic studies in our laboratory (Aston-Jones et al., 1986) identified the nucleus prepositus hypoglossi (PrH) in the dorsomedial medulla as a major afferent of the locus coeruleus (LC). In the present studies, the influence of projections from PrH to LC was assessed in anesthetized rats. Focal electrical stimulation of PrH inhibited the spontaneous discharge of 42 of 47 LC neurons; the latency to onset of such inhibition was 19.8 +/- 2.5 msec and its duration was 172.4 +/- 10.4 msec. PrH-evoked inhibition of LC neurons was unaffected by administration of the opiate receptor antagonist naloxone or the alpha 2-receptor antagonist idazoxan but was substantially reduced by systemic picrotoxin, an antagonist of GABA. The GABAA receptor antagonist bicuculline methiodide blocked the inhibition from PrH, whether applied by local microinfusion or iontophoresis into the LC. These results lead us to propose that PrH provides a direct inhibitory synaptic input to LC, for which GABA is the likely transmitter.

Animals↗
PubMed1988

The role of chymase in ionophore-induced histamine release from human pulmonary mast cells.

Human pulmonary mast cells contain the serine proteases tryptase and chymase. Chymase is present in much smaller quantities than tryptase. The definite physiological role of both enzymes remains to be elucidated, angiotensin processing has been proposed as one possible function of chymase. A dose-dependent inhibition of A 23187-induced histamine release from dispersed human lung mast cells was observed after pretreatment with diisopropylfluorophosphate (DFP) or 1-1-tosyamide-2-phenylethyl chloromethyl ketone (TPCK) but not with N-2-p-tosyl-1-lysine chloromethyl ketone (TLCK). In contrast, no inhibition was observed under the same conditions with isolated rat peritoneal mast cells. These results indicate that a chymase is probably an important factor in a late phase of human lung mast cell activation. Current work focuses on the isolation of human lung chymase to further investigate this topic.

Animals↗
PubMed1988

The effect of serine esterase inhibitors on ionophore-induced histamine release from human pulmonary mast cells.

The serine proteases tryptase and chymase are present in human pulmonary mast cells. About 10-100 times more tryptase than chymase is found in these cells. However, a clear physiological role for both enzymes remains to be elucidated; angiotensin processing has been proposed as one possible function of chymase. A dose-dependent inhibition of A23187-induced histamine release from dispersed human lung mast cells was observed after pretreatment with the serine protease inhibitor diisopropylfluorophosphate (DFP) or the chymotrypsin-like enzyme inhibitor N-tosyl-L-phenylalanine chloromethylketone (TPCK) but not with the trypsin-like enzyme inhibitor N-tosyl-L-lysine chloromethylketone (TLCK). These results indicate that a chymase is probably an important factor in a late phase of human lung mast cell activation.

Calcimycin↗
PubMed1988

Prediction of risk for pseudoallergic reactions and histamine release in patients undergoing anaesthesia and surgery: a computer-aided model using independence-Bayes.

A computer-aided model for the prediction of pseudoallergic reactions was developed using prospective data collected from 581 patients in a controlled clinical trial examining pseudoallergic reactions to the plasma substitute Haemaccel (outdated formulation). The multivariate analysis of 22 proposed risk factors was performed using Bayes theorem. This enabled the accurate prediction of 86% of the patients who had a systemic reaction. The clinical use of such system would enable a selection of patients to receive the effective prophylactic measure of pretreatment with H1 plus H2-receptor antagonists.

Anesthesia↗
PubMed1988

Activation of locus coeruleus from nucleus paragigantocellularis: a new excitatory amino acid pathway in brain.

Recent anatomic and physiologic experiments revealed that a major afferent to the nucleus locus coeruleus (LC) is the nucleus paragigantocellularis (PGi) in the rostral ventrolateral medulla (Aston-Jones et al., 1986). In the present studies, responses of LC neurons to electrical activation of PGi were characterized in anesthetized rats. Low-intensity stimulation of PGi synaptically activated 73% of LC neurons at short latencies (mean onset, 11.3 msec), while a smaller population (16%) of LC neurons exhibited purely inhibitory responses. The excitatory transmission from PGi to LC was pharmacologically analyzed, revealing it to be resistant to cholinergic receptor antagonism, but completely abolished by the excitatory amino acid (EAA) antagonists kynurenic acid and gamma-D-glutamylglycine. The specific N-methyl-D-aspartate antagonist 2--amino-7-phosphonoheptanoic acid (AP7) and the preferential quisqualate receptor antagonist glutamate diethyl ester (GDEE) did not block LC responses to PGi stimulation, leading us to the tentative conclusion that EAAs may operate primarily at a kainate-type receptor on LC neurons to effect excitation from PGi. In addition to their blockade of PGi-evoked activity, kynurenic acid and DGG exerted a similar, simultaneous blockade of the characteristic excitation of LC neurons evoked by electrical stimulation of the hindpaw. These and other results indicate that the proposed EAA pathway from PGi may serve as a final link in a variety of sensory inputs to LC.

Amino Acids↗
PubMed1987

Two physiologically distinct populations of neurons in the ventrolateral medulla innervate the locus coeruleus.

Recent anatomic studies indicate that the nucleus paragigantocellularis (PGi), located in the rostral ventrolateral medulla, strongly innervates the locus coeruleus (LC) while no such input derives from the more caudally located lateral reticular nucleus (LRN). In the present study, focal electrical stimulation of the LC was used to antidromically activate neurons in the ventrolateral medulla. A substantial number of PGi neurons were antidromically driven from the ipsilateral LC, while antidromic activation was virtually absent in LRN. Furthermore, several physiologic properties of antidromically driven cells in PGi define two populations within this group of neurons afferent to LC. These findings provide physiologic confirmation of an anatomically identified input to LC.

Animals↗
PubMed1987

Isolation of mast cells from rabbit lung and liver: comparison of histamine release induced by the hypnotics Althesin and propanidid.

The enzyme collagenase was used to disperse rabbit lung and liver into their component cells. The resulting cell suspensions contained ca. 6.9% (lung) or 6.5% (liver) mast cells and were used in studies of histamine release without further purification. Both cell suspensions exhibited a low spontaneous release of histamine (ca. 6.6% lung, ca. 7.2% liver). Both cell types responded to challenge with anti-rabbit serum with a maximum release of the amine of ca. 22% (lung) and ca. 45% (liver). Concanavalin A challenge generally resulted in bell-shaped dose response curves, however some lung preparations did not respond. The rabbit cells were refractory to stimulation by Compound 48/80 and dextran. However a dose-dependent release of histamine was elicited after challenge with the detergents cremophor El, TN (12-hydroxystearic acid polymerized with ethylene oxide, degree of polymerization 15) and the hypnotics Althesin and propanidid. The maximum release observed depended on which cell preparation had been used. These results further emphasize the functional heterogeneity of mast cells from both different species and from different organs within the same species.

Alfaxalone Alfadolone Mixture↗
PubMed1986

A potent excitatory input to the nucleus locus coeruleus from the ventrolateral medulla.

Our recent anatomic experiments reveal major innervation of the nucleus locus coeruleus (LC) from the nucleus paragigantocellularis (PGi), located in the rostral ventrolateral medulla. In the present studies, low intensity, single pulse electrical stimulation of the PGi synaptically activated most LC neurons examined (69%), while a smaller percentage of LC cells (20%) exhibited pure inhibitory responses. Pharmacologic experiments suggest that the excitatory response may be mediated by an amino acid transmitter.

Amino Acids↗
PubMed1986

The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network.

Dense, focal injections of wheat germ agglutinin conjugated-horseradish peroxidase in the locus coeruleus of rats labeled afferent neurons in unexpectedly few brain regions. Major inputs emanate from only two nuclei--the paragigantocellularis and the prepositus hypoglossi, both in the rostral medulla. The dorsal cap of the paraventricular hypothalamic nucleus and the spinal intermediate gray are possible minor afferents to locus coeruleus. Other areas reported to project to locus coeruleus (for example, amygdala, nucleus tractus solitarius, and spinal dorsal horn) did not exhibit consistent retrograde labeling. Anterograde tracing and electrophysiologic experiments confirmed the absence of input to locus coeruleus from these areas, which instead terminate in targets adjacent to locus coeruleus. These findings redefine the anatomic organization of the locus coeruleus, and have implications for hypotheses concerning the functions of this noradrenergic brain nucleus.

Afferent Pathways↗
PubMed1986

Evidence for self- and neighbor-mediated postactivation inhibition of locus coeruleus neurons.

Activation of locus coeruleus (LC) neurons is typically followed by inhibition of impulse activity lasting hundreds of ms. Previous studies have implicated two possible mechanisms for this postactivation inhibition: collateral synaptic interactions among LC neurons; and spike-induced, calcium-activated potassium conductance in the soma-dendritic membrane of LC cells. In the present study, antidromic or sensory stimuli were presented at near-threshold intensities for activation of LC neurons. A special computer program accumulated activity for trials yielding driven responses separately from that for trials of identical stimuli during the same train that failed to evoke activity. We found significant inhibition of LC impulse activity for antidromic or sensory stimuli that failed to excite the recorded cell as well as for stimuli that activated the recorded cell. The former result precludes an essential role of intrinsic inhibitory membrane currents (e.g. calcium-activated potassium conductance) in generating postactivation inhibition. Administration of the alpha antagonist piperoxane reduced the magnitude of inhibition on both driven and non-driven trials. Our findings indicate that inhibition on non-driven trials appears to be a synaptically mediated phenomenon, perhaps reflecting norepinephrine released from neighboring LC neurons that are activated. Furthermore, our data support the presence of a spike-dependent mechanism that also contributes substantially to postactivation inhibition in these cells. Thus, the overall results indicate the presence of two intracoerulear mechanisms that mediate postactivation inhibition characteristic of noradrenergic LC neurons.

Adrenergic Fibers↗
PubMed1986

Modulation of histamine release from rat peritoneal mast cells by non-cytotoxic concentrations of the detergents Cremophor El (oxethylated castor oil) and Triton X100. A possible explanation for unexpected adverse drug reactions?

Clinically relevant histamine release caused by drugs and/or their solvents is a well known phenomenon. The mechanisms whereby these reactions occur are largely unknown. It was thought that the solubilizing agents potentiate the histamine release elicited by the drugs. Therefore the ability of the two detergents, Cremophor El and Triton X100, to modulate histamine release from rat peritoneal mast cells was examined. Both detergents were used in concentrations that did not themselves induce histamine release. The addition of the detergents to incubation media containing compound 48/80 (0.1 microgram/ml) elevated the release considerably (48/80 alone = 16.2 +/- 2.1% (n = 3); plus Cremophor El (5%) = 41.1 +/- 3.3% (n = 4); plus Triton X100 (0.02 microliter/ml) = 39.7 +/- 3.9% (n = 3); plus Triton X100 (0.01 microliter/ml) = 33.4 +/- 5.0% (n = 3)). In contrast, histamine release induced by Concanavalin A or the calcium ionophore A 23187 was inhibited by both detergents. Thus low concentrations of detergents appear to have a dual role, with both potentiation and inhibition of histamine release being observed. Surgical patients receive many drugs, some soluble in aqueous solutions, others only with the aid of solubilizing agents. 'Hangover effects' due to different plasma half lives, may therefore cause a seemingly harmless drug to act as a histamine liberator. It is therefore important to examine the action of clinically used solvents on histamine liberation caused by therapeutic agents, in order to gain a further understanding of the reaction mechanisms of adverse reactions to drugs.

Animals↗
PubMed1985

Comparison of the histamine-releasing activity of cremophor E1 and some of its derivatives in two experimental models: the in vivo anaesthetized dog and in vitro rat peritoneal mast cells.

Histamine release caused by drugs and/or their solvents in clinical conditions is a well documented observation but the mechanism of this reaction is poorly understood. Hence in this study, the histamine releasing ability of cremophor E1 and six derivatives of 12-hydroxystearic acid (12-HSA) were compared in two models: the in vivo anaesthetized dog and the in vitro isolated rat peritoneal mast cells. The results obtained in both systems differed markedly. Only one compound DH (the diester of 12-HSA with polyethylene glycol) released histamine in both systems. The two substances, which exhibited the weakest histamine releasing ability in the dog model (almost inactive at the doses given) were powerful releasers of histamine from rat peritoneal mast cells (TN, 12-HSA polymerized with ethylene oxide; and ME, the monoester of 12-HSA esterified with polyethylene glycol). The release of histamine from rat peritoneal mast cells was potentiated as the temperature was elevated above 37 degrees C. Due to the heterogeneity of mast cells from both different species and different tissues in the same animal, it is important to choose the appropriate predictive model for clinically important adverse reactions to drugs and/or their solvents. Agents which release histamine by non-specific mechanisms are not uninteresting for the clinical situation.

Animals↗
PubMed1985

Modulation of histamine release by fatty acids. A new in vitro model investigating adverse drug reactions in various species.

Histamine release caused by drugs and/or their solvents is a well known phenomenon. In this study, both in vivo (anaesthetized and conscious dogs) and in vitro (isolated rat peritoneal, human and guinea-pig lung mast cells) models were used. Cremophor E1 and six derivatives of 12-hydroxystearic acid were compared for their histamine releasing abilities. Although the three types of isolated mast cells responded similarly, histamine release being observed with DH (the diester of 12-hydroxystearic acid with polyethylene glycol), TN (12-hydroxystearic acid polymerized with ethylene oxide) and ME (the monoester of 12-hydroxystearic acid esterified with polyethylene glycol), the anaesthetized dog exhibited elevated blood histamine levels and clinical symptoms after administration of all the solubilizing agents, except TN and ME. The reasons for this discrepancy are not known. The addition of the drugs (Althesin or propanidid) to their solubilizing agents caused histamine release, which was not observed with the solubilizing agent alone. This is the first demonstration of an in vitro model, which copies the clinical situation, i.e. solvent does nothing but the solvent plus drug combination causes histamine release and hence adverse reactions.

Alfaxalone Alfadolone Mixture↗
PubMed1984

Prostaglandin and histamine release from stimulated rat peritoneal mast cells.

The production of five prostanoids (PGD2, PGE2, PGF2 alpha, 6-oxo-PGF1 alpha, and TxB2) was examined after mast cell activation. Prostaglandin D2 (PGD2) was the major prostanoid produced after stimulation of rat peritoneal mast cells with the calcium ionophore A 23187, compound 48/80 or anti-rat IgE. The amount of PGD2 generated was not dependent on the quantity of histamine released. The time course of PGD2 production paralleled the release of histamine following activation with A 23187 or anti-rat IgE but with compound 48/80 release of histamine reached a maximum within 15 sec, whereas production of PGD2 was apparent only after 5 min and was still increasing at 30 min.

Animals↗