Action of an opiate receptor blocker on ovine cardiopulmonary responses to endotoxin

Traber, D. L.; Thomson, Philip D.; Blalock, J. Edwin; Smith, E. M.; Adams, T.; Sziebert, L.; Traber, Lillian D.

doi:10.1152/ajpheart.1983.245.2.h189

Cited by 3 publications

(4 citation statements)

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“…This first arose over 30 years ago through the recognition that naloxone and naltrexone could block effects of lipopolysaccharide (LPS, component of endotoxin from the cell walls of gram negative bacteria) [18, 19], now considered as a prototypic TLR4 agonist. Interestingly, recognition that naloxone/naltrexone blocked LPS effects pre-dated the 1998 discovery of TLR4 by close to two decades [20, 21].…”

Section: How Did a Focus On Tlr4 Arise?mentioning

confidence: 99%

Targeting the Toll of Drug Abuse: The Translational Potential of Toll-Like Receptor 4

Bachtell

Hutchinson²,

Wang³

et al. 2015

CNSNDDT

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There is growing recognition that glial proinflammatory activation importantly contributes to the rewarding and reinforcing effects of a variety of drugs of abuse, including cocaine, methamphetamine, opioids, and alcohol. It has recently been proposed that glia are recognizing, and becoming activated by, such drugs as a CNS immunological response to these agents being xenobiotics; that is, substances foreign to the brain. Activation of glia, primarily microglia, by various drugs of abuse occurs via toll like receptor 4 (TLR4). The detection of such xenobiotics by TLR4 results in the release of glial neuroexcitatory and neurotoxic substances. These glial products of TLR4 activation enhance neuronal excitability within brain reward circuitry, thereby enhancing their rewarding and reinforcing effects. Indeed, selective pharmacological blockade of TLR4 activation, such as with the non-opioid TLR4 antagonist (+)-naltrexone, suppresses a number of indices of drug reward/reinforcement. These include: conditioned place preference, self-administration, drug-primed reinstatement, incubation of craving, and elevations of nucleus accumbens shell dopamine. Notably, TLR4 blockade fails to alter self-administration of food, indicative of a selective effect on drugs of abuse. Genetic disruption of TLR4 signaling recapitulates the effects of pharmacological TLR4 blockade, providing converging lines of evidence of a central importance of TLR4. Taken together, multiple lines of evidence converge to raise TLR4 as a promising therapeutic target for drug abuse.

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Section: How Did a Focus On Tlr4 Arise?mentioning

confidence: 99%

Targeting the Toll of Drug Abuse: The Translational Potential of Toll-Like Receptor 4

Bachtell

Hutchinson²,

Wang³

et al. 2015

CNSNDDT

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“…These findings suggest that leukocyte-derived endorphins may be involved in LPS shock and gram-negative sepsis. As mentioned, several reports have demonstrated that lymphocyte depletion of sheep and subsequent injection of E. coli endotoxin results in an abrogation of parts of the resulting pathophysiological response (3,22,23). This abrogation is similar to that seen after naloxone administration to intact animals (8, 9).…”

Section: Resultsmentioning

confidence: 72%

“…This implication was a result of the ability of a potent opiate antagonist, naloxone, to alleviate endotoxininduced hypotension and hyperthermia by apparently blocking the effector molecule (8,15). Additionally, naloxone treatment improved survival rates (17), and plasma endorphin levels have been shown to rise significantly in sheep injected with Escherichia coli endotoxin (lipopolysaccharide [LPS]) (5,23). Results of depletion studies have indicated that leukocytes may also mediate some of the aforementioned endotoxin effects (3,22).…”

mentioning

confidence: 99%

Bacterial lipopolysaccharide induction of leukocyte-derived corticotropin and endorphins

Harbour-McMenamin¹,

Smith²,

Blalock³

1985

Infect Immun

116

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Previous reports have shown that there is an endogenous opioid component associated with pathophysiological responses to endotoxin. It has been shown that these responses are alleviated by naloxone, a specific opiate antagonist. Results of another study have indicated that leukocytes may mediate some of those responses since leukocyte depletion alleviated the effects of lipopolysaccharide. In view of the above reports as well as the finding that leukocytes produce immunoreactive (ir-) endorphins and corticotropin (ACTH) when stimulated with Newcastle disease virus or ACTH-releasing factor, we postulated that leukocytes may serve as an extrapituitary source of endorphins produced in response to bacterial endotoxin. To test this hypothesis, human peripheral blood leukocytes as well as mouse spleen cells were cultured in vitro with Escherichia coli lipopolysaccharide for 48 h. The lipopolysaccharide (i.e., endotoxin) was shown to induce de novo synthesis of ir-ACTH and ir-endorphins. The leukocyte-derived ir-ACTH had a molecular weight of approximately 2,900 and demonstrated a bioactivity similar to that of pituitary-derived ACTH. The lymphocyte-derived irendorphin comigrated with a-and y-endorphin at approximately 1,800 daltons and was shown to bind to brain opiate receptors. These findings imply that leukocyte-derived endorphins may be involved in the pathophysiological response to endotoxin.

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“…Endogenous opiate peptides are elevated during severe stress and also in neurogenic shock. Opiates have shown to have a direct myocardial depressant effect [62][63][64]. Some studies have shown that hemodynamic collapse during shock and cardiac failure can be attenuated by using opioid antagonists [65][66][67].…”

Section: Pathophysiology Of Cardiac Contractility Dysfunctionmentioning

confidence: 99%

Cardiovascular Manifestations of Acute Intracranial Lesions: Pathophysiology, Manifestations, and Treatment

Arab

Yahia

Qureshi

2003

J Intensive Care Med

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The objective of this article was to review the effects of acute intracranial lesions on myocardial function. The authors reviewed scientific and clinical literature retrieved from a computerized MEDLINE search from January 1965 through January 2002. Pertinent literature was referenced, including clinical and laboratory investigations, to demonstrate the effects of acute intracranial lesions on the cardiovascular system. The literature was reviewed to summarize the mechanisms of cardiac damage and clinical manifestations and treatment of cardiovascular dysfunction caused by acute intracranial lesions. Myocardial damage and rhythm disturbances were shown to occur with acute intracranial neurological disease. The subgroup of patients used in this study formed a substantial pool of cardiac donors for cardiac transplantation. The pathophysiology of myocardial dysfunction and the optimal management continues to be a source of debate. In this article, the authors will review the anatomy, the available evidence of the pathophysiology, and the management of this complex group of patients. They will also discuss areas that need to be further investigated. Cardiovascular effects of acute intracranial lesions are common and contribute to increased morbidity and mortality.

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Action of an opiate receptor blocker on ovine cardiopulmonary responses to endotoxin

Cited by 3 publications

References 0 publications

Targeting the Toll of Drug Abuse: The Translational Potential of Toll-Like Receptor 4

Targeting the Toll of Drug Abuse: The Translational Potential of Toll-Like Receptor 4

Bacterial lipopolysaccharide induction of leukocyte-derived corticotropin and endorphins

Cardiovascular Manifestations of Acute Intracranial Lesions: Pathophysiology, Manifestations, and Treatment

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