Uptake and efflux of the peptidic delta-opioid receptor agonist [D-penicillamine2,5]-enkephalin at the murine blood–brain barrier by in situ perfusion
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The pruritus of cholestasis: From bile acids to opiate agonists: Relevant after all these years
2018, Medical HypothesesCitation Excerpt :The reason for increased opioidergic tone in cholestasis is unknown; however, there is evidence to suggest that the liver may contribute to the alterations in the opioid system in cholestasis: (i) the expression of the mRNA of the gene that codes for Met and Leu-enkephalins and for enkephalin containing endogenous opioids, preproenkephalin mRNA, in the cholestatic rat liver, suggesting that the liver may produce endogenous opioids de novo in cholestasis [20], (ii) the significantly higher concentrations of two pentapeptide endogenous opioids, Met-enkephalin and Leu-enkephalin, and that of Met-enkephalin containing opioids in extracts from rat livers with cholestasis from bile duct resection, as compared to that from livers from sham resected controls [21], (iii) the increase in the serum concentration of Met-enkephalin in animals models of cholestasis [22] and in some patients with liver disease [2,23], and [4] by the expression of hepatic Met-enkephalin immunoreactivity in the liver of patients with liver disease including PBC and chronic hepatitis C [24,25], and by its detection in bile [26], suggesting that the liver can accumulate and excrete endogenous opioids in pathological conditions. Whether these findings relate to the increased opioidergic tone in cholestasis, is unknown; however, proteins that can transport opiates in ex vivo experiments, can be found in the basolateral domain of the hepatocyte, choroid plexus, and the blood–brain barrier [27]; accordingly, it is possible that these transporters can transport periphery-derived opioids (e.g. made in the liver) into the central nervous system (CNS). In addition, it has been reported that increased availability of opioid peptides in the periphery, as may be the case in cholestasis, may facilitate their entrance into the CNS [28].
Peptides at the blood brain barrier: Knowing me knowing you
2015, PeptidesCitation Excerpt :Of particular interest to us were the studies that showed that inflammation could regulate the activity and expression of efflux transporters, most notably P-glycoprotein (Pgp), which is the major efflux transporter for morphine and opioid analgesics [90,91]. This interest was driven primarily due to the role of Pgp in limiting opioid peptide delivery [92], thus was a link to our earlier focus on opioid peptide transport. Furthermore, Dr. David Miller's group at the NIEHS described a series of elegant studies that demonstrated the role of Pgp in the efflux transport of a range of substances, and also demonstrated a series of signaling mechanisms that regulated the transport, which included several inflammatory processes (reviewed in [93]).
Delivery of therapeutic peptides and proteins to the CNS
2014, Advances in PharmacologyBlood-brain barrier transport of naloxone does not involve P-glycoprotein-mediated efflux
2010, Journal of Pharmaceutical SciencesP-glycoprotein deficient mouse in situ blood-brain barrier permeability and its prediction using an in combo PAMPA model
2009, European Journal of Pharmaceutical Sciences