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Full-Text Articles in Medicine and Health Sciences
Pivotal Role Of The A2a-Adrenoceptor In Producing Inflammation And Organ Injury In A Rat Model Of Sepsis, Michael Miksa, Padmalaya Des, Mian Zhou, Rongqian Wu, Weifeng Dong, Youxin Ji, Sanna M. Goyert, Thanjavur S. Ravikumar, Ping Wang
Pivotal Role Of The A2a-Adrenoceptor In Producing Inflammation And Organ Injury In A Rat Model Of Sepsis, Michael Miksa, Padmalaya Des, Mian Zhou, Rongqian Wu, Weifeng Dong, Youxin Ji, Sanna M. Goyert, Thanjavur S. Ravikumar, Ping Wang
Publications and Research
Background: Norepinephrine (NE) modulates the responsiveness of macrophages to proinflammatory stimuli through the activation of adrenergic receptors (ARs). Being part of the stress response, early increases of NE in sepsis sustain adverse systemic inflammatory responses. The intestine is an important source of NE release in the early stage of cecal ligation and puncture (CLP)-induced sepsis in rats, which then stimulates TNF-a production in Kupffer cells (KCs) through the activation of the a2-AR. It is important to know which of the three a2-AR subtypes (i.e., a2A, a2B or a2C) is responsible for the upregulation of TNF-a production. The aim of this …
Naloxone's Pentapeptide Binding Site On Filamin A Blocks Mu Opioid Receptor–Gs Coupling And Creb Activation Of Acute Morphine, Hoau-Yan Wang, Lindsay H. Burns
Naloxone's Pentapeptide Binding Site On Filamin A Blocks Mu Opioid Receptor–Gs Coupling And Creb Activation Of Acute Morphine, Hoau-Yan Wang, Lindsay H. Burns
Publications and Research
Chronic morphine causes the mu opioid receptor (MOR) to switch its coupling from Gi/o to Gs, resulting in excitatory signaling via both Gαs and its Gβγ dimer. Ultra-low-dose naloxone (NLX) prevents this switch and attenuates opioid tolerance and dependence. This protective effect is mediated via a high-affinity interaction of NLX to a pentapeptide region in c-terminal filamin A (FLNA), a scaffolding protein interacting with MOR. In organotypic striatal slice cultures, we now show that acute morphine induces a dose-dependent Go-to-Gs coupling switch at 5 and 15 min that resolves by 1 hr. The acute Gs coupling induced by 100 µM …