Relationships between membrane cholesterol, α-adrenergic receptors, and platelet function

Insel, Paul A.; Nirenberg, Peter; Turnbull, Judy; Shattil, Sanford J.

doi:10.1021/bi00617a029

Cited by 84 publications

(27 citation statements)

References 30 publications

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“…Platelets possess a-adrenergic receptors28 29 and the interaction of epinephrine with these receptors initiates platelet aggregation.28' 29 Alexander et al 28 postulated that these receptors are regulated by changes in the circulating levels of a agonists. Kaplan et al showed that epinephrine at supraphysiologic levels in vitro causes PF4 and BTG release.…”

Section: Plasma Epinephrine and Norepinephrine During Treadmill Exercisementioning

confidence: 99%

Studies of platelet factor 4 and beta thromboglobulin release during exercise: lack of relationship to myocardial ischemia.

Stratton¹,

Malpass²,

Ritchie³

et al. 1982

Circulation

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SUMMARY Platelet activation, which results in release of the platelet-specific proteins platelet factor 4 (PF4) and BTG thromboglobulin (BTG), may participate in exercise-induced myocardial ischemia by the formation of intravascular platelet aggregates or the generation of vasoactive substances such as thromboxane A2. We sought to determine if platelet release occurs during exercise-induced ntyocardial ischemia and its relationship to exercise-induced catecholamine release in 10 normal males (mean age 29 + 6 years) and 25 males with proved coronary artery disease (mean age 60 ± 8 years) who performed maximal, symptomlimited treadmill exercise tests. None of the subjects took drugs known to modify platelet behavior; 17 coronary artery disease patients took B-blocking agents. Plasma and urine PF4, plasma BTG and plasma catecholamines were measured before and immediately after exercise. Plasma PF4 and BTG were also measured 30 minutes after exercise. Ischemia, defined as angina or 1 mm or more of horizontal or downsloping ST depression, developed in 14 coronary artery disease patients.In young normal subjects during exercise, plasma PF4 increased from 2.1 ± 1.2 at rest to 4.7 ± 2.6 ng/ml at maximal exercise (p < 0.01 rest vs exercise) and plasma BTG increased from 11.7 ± 5.4 to 16.7 ± 7.7 ng/ ml (p < 0.01 rest vs exercise). Among the 25 coronary artery disease patients, plasma PF4 during exercise increased slightly but significantly, from 2.1 1.4 at rest to 2.6 ± 2.2 ng/ml at exercise (p < 0.01); plasma BTG did not change significantly, from 13.3 6.0 at rest to 14.1 ± 5.8 ng/ml during exercise. The small exercise-induced elevations in plasma PF4 and BTG in all 25 coronary artery disease patients were significantly less than those in the 10 young normal subjects (both p < 0.01 vs normals). Among the subset of 14 coronary artery disease patients with exercise-induced ischemia, neither plasma PF4 nor BTG increased significantly (PF4 from 2.6 1.7 at rest to 3.0 ± 2.9 ng/ml with exercise; plasma BTG from 13.6 ± 6.4 to 14.1 ± 7.1 ng/ml). The 14 coronary artery disease patients with ischemia had less exercise-induced elevation in both plasma PF4 and BTG than normal subjects (both p < 0.05). Plasma PF4 and BTG levels 30 minutes after exercise were not significantly different from rest levels in any subject group. Mean rest, peak exercise, and 30-minute postexercise plasma PF4 and BTG values did not differ significantly between the 17 coronary disease patients taking B-blocking agents and the eight coronary disease patients not taking Bblocking drugs. Furthermore, urinary PF4 did not change significantly with exercise in either norrmal subjects or in any of the coronary artery disease groups. Among all 35 subjects, exercise-induced increases in plasma epinephrine correlated with increases in plasma PF4 (r = 0.35; p = 0.04) and BTG (r = 0.40; p = 0.02). Increases in norepinephrine did not correlate with either increases in plasma PF4 (r = 0.24, p = 0.2) or BTG (r 0.23, p = 0.2).We conclude that exercise-induced release of pl...

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Section: Plasma Epinephrine and Norepinephrine During Treadmill Exercisementioning

confidence: 99%

Studies of platelet factor 4 and beta thromboglobulin release during exercise: lack of relationship to myocardial ischemia.

Stratton¹,

Malpass²,

Ritchie³

et al. 1982

Circulation

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“…Penicillin G was more potent than carbenicillin in that it inhibited the initial rate of aggregation half-maximally at 14 mM, the aggregation amplitude at 2.5 mM (Fig. 1 acteristic of the a-adrenergic receptor (11,17,18). At concentrations ofantibiotic that inhibited epinephrineinduced platelet function by more than 80%, carbenicillin (36 mM) and penicillin G (31 mM) did not change the maximum number of 3H-DHE binding sites per platelet (Fig.…”

Section: Resultsmentioning

confidence: 96%

“…Platelets were resuspended in the incubation buffer to a platelet count of 1.5 x 109/ml and mixed with 1/10 vol ofan aqueous solution of either carbenicillin or penicillin G, or with NaCl or KCI as controls. a-adrenergic binding sites on intact platelets were quantitated as described previously (17,18). Briefly, intact platelets (3 x was extracted with ethanol and migrated identically as native 3H-DHE on thin-layer chromatography (18).…”

Section: Methodsmentioning

confidence: 99%

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Carbenicillin and Penicillin G Inhibit Platelet Function In Vitro by Impairing the Interaction of Agonists with the Platelet Surface

Shattil¹,

Bennett²,

McDonough³

et al. 1980

J. Clin. Invest.

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109

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“…Thus, fluidity of platelet membranes affects their sensitivity to the aggregating agent adrenaline (Insel et al, 1978 (Loh & Law, 1980). Nevertheless, the important point is the marked effect of membrane fluidity on 5-HT binding.…”

Section: Mobility Ofproteins and Receptors Within Membranesmentioning

confidence: 99%

Biochemical pharmacology of paradoxical sleep.

Gaillard¹

1983

Brit J Clinical Pharma

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1 The role of noradrenergic cells in the regulation of paradoxical sleep is still controversial, and experimental data have given rise to contradictory interpretations.2 Early investigations focused primarily on chemical neurotransmissions. However, the process of information transmission between cells involves many other factors, and the cell surface is an important site for transduction of messages into modifications of the activity of postsynaptic cells.3 a-adrenoceptors are believed to play an important role in the control of wakefulness and paradoxical sleep. Experimental evidence suggests that physiological modulation of receptor sensitivity, possibly by specific neuro-modulators, may be a key mechanism in synaptic transmission. 4 In the investigation of the mechanisms involved in paradoxical sleep regulation, lesions of the locus coeruleus have given equivocal results. Collateral inhibition, probably mediated by a2-adrenoceptors, appears to be a powerful mechanism. The exact temporal relationship between noradrenergic cell activation and paradoxical sleep production is not established, but 5-HT appears to be involved. Differences between paradoxical sleep and waking may be related to a physiological modulation of a2-adrenoceptor sensitivity.

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Relationships between membrane cholesterol, α-adrenergic receptors, and platelet function

Cited by 84 publications

References 30 publications

Studies of platelet factor 4 and beta thromboglobulin release during exercise: lack of relationship to myocardial ischemia.

Studies of platelet factor 4 and beta thromboglobulin release during exercise: lack of relationship to myocardial ischemia.

Carbenicillin and Penicillin G Inhibit Platelet Function In Vitro by Impairing the Interaction of Agonists with the Platelet Surface

Biochemical pharmacology of paradoxical sleep.

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