Characterization of the Presence and Function of Platelet Opioid Receptors

Abstract

Opioids are typically used for the treatment of pain related to disease or surgery. In the body, they enter the bloodstream and interact with a variety of immune and neurological cells that express the μ-, δ-, and κ-opioid receptors. One blood-borne cell-like body that is not well understood in the context of opioid interactions is the platelet. The platelet is a highly sensitive anucleate cell-like fragment responsible for maintaining hemostasis through shape change and the secretion of chemical messengers. This research characterizes platelet opioid receptors, how specific receptor agonists impact platelet exocytosis, and the role of the κ-and μ-receptors in platelet function. Platelets were found to express all three opioid receptors, but upon stimulation with their respective agonist no activation was detected. Furthermore, exposure to the opioid agonists did not impact traditional platelet secretion stimulated by thrombin, a natural platelet activator. In addition, data collected from knockout mice suggest that the opioid agonists may be interacting nonspecifically with platelets. Dark-field images revealed differences in activated platelet shape between the κ- and μ-knockout platelets and the control platelets. Finally, κ-knockout platelets showed variations in their ability to adhere and aggregate compared to control platelets. Overall, these data show that platelet function is not likely to be heavily affected by blood-borne opioids.

Interactions of fentanyl with blood platelets and plasma proteins: platelet sensitivity to prasugrel metabolite is not affected by fentanyl under in vitro conditions

“…Also, at therapeutic and supratherapeutic concentrations, fentanyl failed to abolish the inhibitory effect of prasugrel metabolite following ADP-induced platelet activation. Taken together, our data are consistent with those of Gruba et al [ 5 ], who report that stimulation of platelet opioid receptors in wildtype mice by DAMGO, DPDPE, or U-50488, which target the μ-, δ-, and κ-opioid receptors, does not lead to activation of isolated platelets. Likewise, the δ-granule secretion from thrombin-stimulated platelets has been shown to be unaffected by opioid receptor agonists.…”

“…Likewise, the δ-granule secretion from thrombin-stimulated platelets has been shown to be unaffected by opioid receptor agonists. Based on all collected data, it has been postulated that opioids, such as morphine or ketamine, do not significantly affect platelet function [ 5 ].…”

“…Until now, the importance of opioid receptors in platelet functioning remains unclear, since no other reports identifying opioid receptors on platelets in humans have been published. Interestingly, μ-, δ-, and κ-opioid receptors have been recently detected in mouse platelets [5]. In addition, several clinical trials (PERSEUS, PACIFY, ON-TIME 3) have consistently demonstrated that fentanyl attenuates the antiplatelet effects of the P2Y 12 inhibitor ticagrelor in patients undergoing percutaneous coronary intervention (PCI) [6][7][8][9].…”

Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma

“…The cells in the device were fed with fresh media every day for 3 to 5 days. A representative image of the platelet adhesion assay can be seen in Figure of our previously described work …”

“…A representative image of the platelet adhesion assay can be seen in Figure 6 of our previously described work. 44 On the day of experiments, platelets (4 × 10 7 platelets/mL) were incubated with 0.5 μM IgE for 2 h and washed at 800g for 5 min after the addition of ADC. The pellet was suspended in 2 mL Tyrode's buffer for a final concentration of ∼2 × 10 7 platelets/mL.…”