Opioid receptor types

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. 

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,... 

North RA. Opioid receptor types and membrane ion channels. Trends Neuro-sci 1986 9 114-117. 

There are three classical opioid receptor types, p, 8, and K 914 Chronic opiate treatment results in complex adaptations in opioid receptor signaling 915... 

There are three classical opioid receptor types, p, 8,... 

Narita M, Funada M, Suzuki T (2001) Regulation of opioid dependence by opioid receptor types. Pharmacol Ther 89 1-15... 

Fig. 9.8 Examples of rule-of-three compliant molecules that have biological activity better than 10 nM. Under each molecule, the following information is included molecule name, MW, ClogP, the biological activity type, value and target. Target names are as follows D3 and D4 - dopaminergic receptor types 2 and 3 AChE and BChE - acetyl- and butyryl-choline esterases PRa and PRb - progesterone receptor types A and B H] and H3, histamine receptor types 1 and 3 5-HT2a, 5-HT2b, 5-HT2c, 5-HT3, 5-HT4 - serotonin receptor subtypes 2A, 2B, 2C, and types 3 and 4 DAT, NET, 5-HTT - dopamine, norepinephrine and serotonin transporter proteins /X], /x.2, S, ki, ks - opioid receptor types mu-1, mu-2, delta, kappa-1 and kappa-3 5a-Rl and 5o -R2 - 5-alpha-reductase isozymes 1 and 2 Flt-1-fms-like tyrosine kinase receptor.

C. The purpose of this question is to clarify the functional significance of the activation of opioid receptor types. Respiratory depression and bradycardia are associated with the ji2-opioid receptor. Mydriasis is associated with the o-receptor, which is no longer thought of as opioid. Opioids, via respiratory depression, induce hypercapnia, a build-up of carbon dioxide. The clinically relevant sign of opioid overdose and opioid use is miosis, pinpoint pupils, mediated by K-receptor activation. 

ORL1- receptor More recently, a fourth opioid receptor type, named ORL1-... 

Fleetwood-Walker, S. M., Mitchell, R., Hope, P. J., El-Yassir, N., Molony, V. The roles of tachykinin and opioid receptor types in nociceptive and non-nociceptive processing in superficial dorsal horn. In Fine afferent nerve fibers and pain, 1987, edited by R. F. Schmidt, H. G. Schaible, C. Vahle-Hinz, 239-247, VCH, Weinheim. 

Zaki PA, Bilsky EJ, Vanderah TW, Lai J, Evans CJ, Porreca F. Opioid receptor types and subtypes the delta receptor as a model. Annu Rev Pharmacol Toxicol 1996 36 379-401. 

Daniels DJ, Kulkarni A, Portoghese PS. Bivalent ligands designed to probe receptor heterodimers/hetero-oligomers pharmacological evidence for interactions between opioid receptor types. International Narcotic Research Conference, Monterey, CA, 2002 S47. 

In its compact crystal structure, the two opioid tetrapeptide pharmacophores of biphalin are not conformationally equivalent. One tetrapeptide, which has a steric similarity with the delta-selective peptide DADLE, folds into a random coil. The contralateral tetrapeptide, sterically similar to the mu-selective peptide D-TIPP-NH2, exhibits a fairly normal type III (3 bend [4]- These conformational features suggest that under physiological conditions, biphalin may easily bind to these respective opioid receptors. This duality of binding affinity is probably the reason that biphalin is able to interact with all opioid receptor types. 

Recent investigations have revealed that the delta opioid receptor also is involved in the modulation of gastrointestinal functions, particularly in mammals other than the guinea pig. In this chapter, we will discuss the presence and roles of this opioid receptor type in mediating the actions of opioid drugs and their endogenous counterparts in the digestive tract. 

The body of literature concerning the functional roles of delta opioid receptors in the digestive tract is somewhat complicated by the results of studies that employed opioid agonists or antagonists with relatively poor selectivity for opioid receptor types (e.g., capable of interacting with both delta and mu opioid receptors within a narrow concentration range). Such ligands include... 

Opioid agonists, administered into the cerebral ventricles of anesthetized rodents and conscious dogs, increase basal fluid absorption or decrease fluid accumulation evoked by cholera toxin in small intestinal loops [135— 138]. Experiments with drugs selective for each opioid receptor type revealed that these effects are mediated predominantly by central mu opioid receptors with little involvement of delta opioid receptors [137-139]. 

Chlornaltrexamine (/f-CNA, 15) another naltrexone derivative modified at C-6, is a nonequilibrium antagonist which blocks irreversibly the three major opioid receptor types (ji, k and 8). Portoghese and his collaborators have developed this compound as the first affinity labelling agent of its class [58-61]. Compound (15) has an alkylating function at C-6 (classic nitrogen mustards) able to bind covalently to opioid receptors. In the tail flick assay in mice, /f-CNA inhibited morphine-induced antinociception for 3-6... 

PertOfran desipramine. pertussis toxin (PTX) is elaborated by a bacterium Bordetella pertussis) and is a hexameric protein (4-5 subunits from A-B complex). It is a G-protein inactivator that binds to the ADP-ribosylation regulatory site of the G/Go family of subunits which couple negatively to adenylyl cyclase. The cellular responses blocked by PTX are varied, and typically include those due to 03 and opioid receptor type activation. The inactivation of this key regulatory unit explains some of the side-effects of whooping cough (caused by Bordetella pertussis) where production of this toxin is a main pathological factor. This toxin is an important pharmacological tool. 

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