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GX/Z Is Regulated by μ But Not δ Opioid Receptors in the Stimulation of the Low K m GTPase Activity in Mouse Periaqueductal Grey Matter
Author(s) -
Garzón Javier,
MartinezPeña Yolanda,
SánchezBlázquez Pilar
Publication year - 1997
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 - 10.1111/j.1460-9568.1997.tb01474.x
Subject(s) - damgo , chemistry , gtpase , agonist , stimulation , receptor , medicine , endocrinology , intrinsic activity , enkephalin , g protein , internalization , μ opioid receptor , opioid receptor , opioid , biochemistry , biology
High affinity low K m GTPase activity was measured in membrane preparations of adult mouse mesencephalic periaqueductal grey matter (PAG). Opioids displaying selectivity towards μ‐ or δ‐opioid receptors (OR) activated the enzyme in a concentration‐dependent manner. Antibodies to μ‐OR greatly impaired the potential of μ‐agonists, [D‐Ala 2 ,N‐MePhe 4 ,Gly‐ol 5 ]‐enkephalin (DAMGO) and morphine, to increase hydrolysis of GTP. The same antibodies had little effect on [D‐Pen 2,5 ]enkephalin (DPDPE) and [D‐Ala 2 ]deltorphin II, both agonists at δ‐OR. Stimulation of GTPase by DPDPE and [D‐Ala 2 ]deltorphin II ‐ but not by morphine or DAMGO ‐ was diminished by antibodies to δ‐OR. The blockade of G i2 α subunits by specific antibodies impaired the activation of Gα‐related GTPase by all opioids. Antibodies in vitro, and oligodeoxynucleotides in vivo, prepared against Gx/zα subunits, reduced the release of Pi promoted by DAMGO and morphine. The impairment of Gx/z proteins also slightly reduced the effect of the δ2 agonist [D‐Ala 2 ]deltorphin II. At δ1 receptors, DPDPE fully expressed its activation of GTPase. These results indicate that in the PAG, μ‐OR and δ‐OR couple with Gi2 transducer proteins. Notably, μ‐OR also regulates the pertussis toxin‐insensitive G‐protein Gx/z, an effect poorly exhibited by δ‐OR in this tissue.