Opioid receptor studies

The [nC]BPN is ready for use in cerebral opioid receptor studies by PET within 24 minutes from EOB, including radiosynthesis, purifications, formulation for in vivo injection and specific-activity determination266. 

The opioid peptides vary in their binding affinities for the multiple opioid receptor types. Leu- and Met-enkephalin have a higher affinity for 5-receptors than for the other opioid receptor types (68), whereas the dynorphin peptides have a higher affinity for K-sites (69). P-Endorphin binds with equal affinity to both p- and 5-receptors, but binds with lower affinity to K-sites (70). The existence of a P-endorphin-selective receptor, the S-receptor, has been postulated whether this site is actually a separate P-endorphin-selective receptor or is a subtype of a classical opioid receptor is a matter of controversy (71,72). The existence of opioid receptor subtypes in general is quite controversial although there is some evidence for subtypes of p- (73), 5-(74), and K-receptors (72,75), confirmation of which may be obtained by future molecular cloning studies. 

Cytotoxics cause an elevation of dopamine levels in the area postrema in animal studies and may release prostaglandins and inhibit enzymes such as enkepha-linases to allow increased levels of enkephalins to activate opioid receptors on dopaminergic nerves. 

They act as analgesics by inhibiting release of nociceptive neurotransmitters from primary afferent terminals as well as by depressing post-synaptic potentials on second order neurons. Opioid receptors are also present on some nociceptors and their expression and peripheral transport is increased upon peripheral inflammation. Peripheral opioid analgesia has been established in animal models. Although clinical studies have yielded mixed results so far, this field holds great promise. Despite side effects, such as euphoria, dysphoria, sedation, respiratory depression and obstipation and tolerance and dependence phenomena which arise upon... 

LAAM (L-a-acetylmethadol or levomethadyl acetate) is a full agonist at the i opioid receptor with pharmacologic properties similar to those of methadone. A number of studies have demonstrated that treatment with LAAM results in reduction of opioid use and beneficial effects comparable to those achieved with methadone (Ling et al. 1978 Tennant et al. 1986 Zangwell et al. 1986). However, retention rates are higher in patients who take methadone doses of 80—100 mg/day. 

Potenza MN, Gold SJ, Roby-Shcmkowitz A, et al Effects of regulators of G protein-signaling proteins on the functional response of the mu-opioid receptor in a mel-anophore-based assay. J Pharmacol Exp Ther 291 482 91, 1999 Quaglio G, Talamini G, Lechi A, et al Study of 2708 heroin-related deaths in northeastern Italy 1985—98 to establish the main causes of death. Addiction 96 1127— 1137, 2001... 

Woody GE, Luborsky L, McLellan AT, et al Psychotherapy for opiate addicts does it help Arch Gen Psychiatry 40 639—645, 1983 Woody GE, McLellan AT, Luborsky L, et al Severity of psychiatric symptoms as a predictor of benefits from psychotherapy the Veterans Administration-Penn study. Am J Psychiatry 141 1172—1177, 1984 Woody GE, McLellan AT, Luborsky L, et al Twelve-month follow-up of psychotherapy for opiate dependence. Am J Psychiatry 144 590-596, 1987 Yabaluri N, Medzihradsky F Down-regulation of mu-opioid receptor by full but not partial agonists is independent of G protein coupling. Mol Pharmacol 52 896-902, 1997... 

Three endogenous opioids have been identified enkephalins, dynorphins and beta-endorphins. These opioid peptides selectively bind to the seven transmembrane GPCRs delta (8), kappa (k), and mu (p). Although dynorphin binds predominately to the k receptor, P-endorphines and enkephalins bind to p and 8 opioid receptors. It is important to note that the analgesia induced by opioids is mediated predominately throngh the p opioid receptor. In vitro studies have shown a decrease in the immnne function and proliferation following p-endorphin administration in rodents (Ray and Cohn 1999) and that the immunosuppressive effects by P-endorphins are steroid-independent (Berkenbosch et al. 1984 Nelson et al. 2000). 

Since initial studies identified opioid receptors on T-lymphocytes (Wybran et al. 1979), the effects of opioids on immune function have been extensively studied. Details of these studies have been exhaustively reviewed (Madden et al. 1991 Adler et al. 1993 Peterson et al. 1998 Donahoe and Vlahov 1998 Roy et al. 2006), and will only be briefly mentioned here. In general, opioids suppress immune function. Peripheral leukocytes, including lymphocytes and peripheral blood mononuclear cells (PBMCs) can express the four major opioid receptor types, MOP, DOP, KOP,... 

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