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Influence of Gz and Gi2 transducer proteins in the affinity of opioid agonists to μ receptors
Author(s) -
Garzón Javier,
Castro Marián,
SánchezBlázquez Pilar
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00267.x
Subject(s) - dadle , chemistry , enkephalin , receptor , damgo , μ opioid receptor , (+) naloxone , g protein , opioid , medicine , opioid peptide , opioid receptor , naltrexone , endocrinology , biochemistry , biology
The affinity displayed by different opioids to μ receptors (ORs) was determined in mouse brain membranes incubated with antibodies directed to Gα subunits of the guanine nucleotide‐binding proteins Gi2 and Gz. Assays were conducted with 10 p m 125 I‐Tyr 27 ‐β‐endorphin in the presence of 300 n m N , N ‐diallyl‐Tyr‐(α‐aminoisobutyric acid) 2 ‐Phe‐Leu‐OH (ICI‐174 864), which prevented the binding of the iodinated neuropeptide to δ‐ORs. Gpp(NH)p or the preincubation of mouse brain membranes with IgGs to G i2 α or G z α subunits, promoted reductions in the affinity exhibited by the labelled probe. The potencies of β‐endorphin, [D‐Ala 2 , N ‐MePhe 4 ,Gly‐ol 5 ]‐enkephalin (DAMGO) and [D‐Pen 2,5 ]enkephalin (DPDPE) were reduced after impairing the coupling of μ‐ORs to Gi2 or Gz proteins. Morphine showed a loss of affinity towards the μ‐OR after preincubation of membranes with IgGs to G z α subunits. However, it retained its potency after treatment with the anti‐G i2 α IgGs. Conversely, [D‐Ala 2 , D‐Leu 5 ]enkephalin (DADLE) and [D‐Ser 2 , Leu 5 ] enkephalin‐Thr 6 (DSLET) showed decreased affinity to μ‐ORs after treatment with anti‐G i2 α IgGs, with no noticeable change following the use of IgGs to G z α subunits. The affinity exhibited by the opioid antagonists naloxone, naltrexone, naloxonazine and [Cys 2 ,Tyr 3 ,Orn 5 ,Pen 7 amide]somatostatin analogue (CTOP) remained unchanged after either treatment. Therefore, the affinity exhibited by opioid agonists of μ‐ORs, but not antagonists, depends on the nature of the G‐protein coupled to these receptors.