Opiate receptors on lymphocytes and platelets in man

Mehrishi, J.N.; Mills, Ivor H.

doi:10.1016/0090-1229(83)90074-0

Cited by 195 publications

(47 citation statements)

References 21 publications

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“…Evidence for the expression of opiate receptors on immune cells, in particular receptors for morphine and the metabolites of heroin, provided a biologic link between opiates and the cells of the human immune system (25,26). Opioid receptors (, , and ␦), as well as nonclassic opioidlike receptors, are present on cells of the human immune system (27)(28)(29)(30). Binding sites for the novel morphine receptor designated 3 are detectable on human peripheral blood isolated monocytes (31).…”

Section: Discussionmentioning

confidence: 99%

Morphine Enhances HIV Infection of Neonatal Macrophages

Merrill

Mooney

et al. 2003

Pediatr Res

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Section: Discussionmentioning

confidence: 99%

Morphine Enhances HIV Infection of Neonatal Macrophages

Merrill

Mooney

et al. 2003

Pediatr Res

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“…62,63 Even if -opioid receptors were present on platelets, one would predict that U50488H would potentiate platelet activation due to stimulation of G i pathways. On the contrary, we observed inhibition of G i -mediated platelet responses by U50488H.…”

Section: Discussionmentioning

confidence: 99%

Role of G protein–gated inwardly rectifying potassium channels in P2Y12 receptor–mediated platelet functional responses

Shankar

Murugappan²,

Kim³

et al. 2004

Blood

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The role of the G i -coupled platelet P2Y 12 receptor in platelet function has been well established. However, the functional effector or effectors contributing directly to ␣IIb␤3 activation in human platelets has not been delineated. As the P2Y 12 receptor has been shown to activate G protein-gated, inwardly rectifying potassium (GIRK) channels, we investigated whether GIRK channels mediate any of the functional responses of the platelet P2Y 12 receptor. Western blot analysis revealed that platelets express GIRK1, GIRK2, and GIRK4. In aspirin-treated and washed human platelets, 2 structurally distinct GIRK inhibitors, SCH23390 (R(؉)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride) and U50488H (trans-(؎)-3,4-dichloro-N-methyl-N-[2-(pyrrolidinyl)cyclohexyl] benzeneacetamide methanesulfonate), inhibited adenosine diphosphate (ADP)-, 2-methylthioADP (2-MeSADP)-, U46619-, and low-dose thrombin-mediated platelet aggregation. However, the GIRK channel inhibitors did not affect platelet aggregation induced by high concentrations of thrombin, AYPGKF, or convulxin. Furthermore, the GIRK channel inhibitors reversed SFLLRN-induced platelet aggregation, inhibited the P2Y 12 -mediated potentiation of dense granule secretion and Akt phosphorylation, and did not affect the agonist-induced G qmediated platelet shape change and intracellular calcium mobilization. Unlike AR-C 69931MX, a P2Y 12 receptor-selective antagonist, the GIRK channel blockers did not affect the ADP-induced adenlylyl cyclase inhibition, indicating that they do not directly antagonize the P2Y 12 receptor. We conclude that GIRK channels are important functional effectors of the P2Y 12 receptor in human platelets. IntroductionPlatelets play an important role in normal hemostasis and abnormal activation of platelets leads to thrombosis. During vascular injury or conditions of high shear, exposure of the collagen-rich subendothelium activates the platelets and results in the formation of a stable thrombus due to the combined action of adenosine diphosphate (ADP) secreted from platelet-dense granules and generated thrombin. 1 Any perturbations in this system can have pathologic cardiovascular implications such as intravascular thrombus formation and vascular occlusion.ADP is an important component of the platelet-dense granules and also an important platelet agonist that stimulates platelets by acting on the G q -coupled P2Y 1 receptor and G i -coupled P2Y 12 receptor. 2,3 Once released, it amplifies the primary responses of other agonists such as collagen and thrombin, leading to enhanced platelet aggregation and stability of the thrombus. 4,5 It is now well established that concomitant signaling through G q -coupled P2Y 1 and G i -coupled P2Y 12 is necessary and sufficient for the integrin GPIIb/IIIa activation. 3 Furthermore, selective G i activation, when coupled with selective G 12/13 stimulation, also results in platelet aggregation. 6,7 Notably, the P2Y 12 -coupled G i signaling is also crucial for potentiating dense...

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“…The existence of opiate receptors on leukocytes is less clear. Mehrishi and Mills (1983) reported the presence of such a receptor, whereas Mendelsohn, Kerchner, Culwell, and Ades (1985) were unable to demonstrate the opiate receptor on lymphocytes.…”

Section: Introductionmentioning

confidence: 98%

Modulation of the immune response by POMC-derived peptides

Heijnen

Zijlstra

Kavelaars

et al. 1987

Brain, Behavior, and Immunity

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The POMC-derived peptides (5endorphin and ACTH are capable of modulating an immune response in physiological concentrations. These neuropeptides can either enhance or inhibit the proliferative response of human peripheral blood lymphocytes after stimulation with the mitogen concanavalin A. The modulatory action of the peptides is not only dependent on the concentration but appears to be donor dependent. The response pattern observed is not determined by a selective affinity for certain amino acid sites on the molecules with "enhancing" or "inhibiting" activities. since fragments of P-endorphin and ACTH also produce a differential donor-dependent response pattern.

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Opiate receptors on lymphocytes and platelets in man

Cited by 195 publications

References 21 publications

Morphine Enhances HIV Infection of Neonatal Macrophages

Morphine Enhances HIV Infection of Neonatal Macrophages

Role of G protein–gated inwardly rectifying potassium channels in P2Y12 receptor–mediated platelet functional responses

Modulation of the immune response by POMC-derived peptides

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