TRPV1 is a physiological regulator of μ-opioid receptors.
نویسندگان
چکیده
Opioids are powerful analgesics, but also carry significant side effects and abuse potential. Here we describe a modulator of the μ-opioid receptor (MOR1), the transient receptor potential channel subfamily vanilloid member 1 (TRPV1). We show that TRPV1 binds MOR1 and blocks opioid-dependent phosphorylation of MOR1 while leaving G protein signaling intact. Phosphorylation of MOR1 initiates recruitment and activation of the β-arrestin pathway, which is responsible for numerous opioid-induced adverse effects, including the development of tolerance and respiratory depression. Phosphorylation stands in contrast to G protein signaling, which is responsible for the analgesic effect of opioids. Calcium influx through TRPV1 causes a calcium/calmodulin-dependent translocation of G protein-coupled receptor kinase 5 (GRK5) away from the plasma membrane, thereby blocking its ability to phosphorylate MOR1. Using TRPV1 to block phosphorylation of MOR1 without affecting G protein signaling is a potential strategy to improve the therapeutic profile of opioids.
منابع مشابه
Functional interaction between TRPV1 and μ-opioid receptors in descending antinociceptive pathway activates glutamate transmission and induces analgesia
The transient receptor potential vanilloid-1 (TRPV1) receptor is involved in peripheral and spinal nociceptive processing and is a therapeutic target for pain. We have shown previously that TRPV1 in the ventrolateral periaqueductal grey (VL-PAG) tonically contributes to brainstem descending antinociception by stimulating glutamate release into the rostral ventromedial medulla and OFF neuron act...
متن کاملModality-specific peripheral antinociceptive effects of μ-opioid agonists on heat and mechanical stimuli: Contribution of sigma-1 receptors
Morphine induces peripherally μ-opioid-mediated antinociception to heat but not to mechanical stimulation. Peripheral sigma-1 receptors tonically inhibit μ-opioid antinociception to mechanical stimuli, but it is unknown whether they modulate μ-opioid heat antinociception. We hypothesized that sigma-1 receptors might play a role in the modality-specific peripheral antinociceptive effects of morp...
متن کاملThe μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway
BACKGROUND The vanilloid receptor 1 (TRPV1) is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA) pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pai...
متن کاملMorphine Reduces Expression of TRPV1 Receptors in the Amygdala but not in the Hippocampus of Male Rats
Background: Chronic use of opioids usually results in physical dependence. The underlying mechanisms for this dependence are still being evaluated. Transient receptor potential vanilloid type 1 (TRPV1) are important receptors of pain perception. Their role during opioid dependence has not been studied well. The aim of this study was to evaluate the effect of morphine-dependence on the expressio...
متن کاملAn Experimental Study on Spinal Cord µ-Opioid and α2-Adrenergic Receptors mRNA Expression Following Stress-Induced Hyperalgesia in Male Rats
Background: Intense stress can change pain perception and induce hyperalgesia; a phenomenon called stress-induced hyperalgesia (SIH). However, the neurobiological mechanism of this effect remains unclear. The present study aimed to investigate the effect of the spinal cord µ-opioid receptors (MOR) and α2-adrenergic receptors (α2-AR) on pain sensation in rats with SIH. Methods: Eighteen Sprague-...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 114 51 شماره
صفحات -
تاریخ انتشار 2017