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PTX‐insensitive Gz transduction pathway contributes to buprenorphine‐induced supraspinal, but not spinal, antinociception
Author(s) -
DING ZHE,
RAFFA ROBERT B
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1125.10
Subject(s) - fentanyl , pharmacology , morphine , (+) naloxone , buprenorphine , opioid , agonist , chemistry , analgesic , antagonist , μ opioid receptor , medicine , receptor , biochemistry
Buprenorphine is known as an opioid analgesic. Although it shares some of the general characteristics of other opioids, it displays preclinical pharmacology and clinical attributes distinct from opioids such as morphine and fentanyl. As a way of elucidating some of the differences, we investigated the contribution of G proteins in buprenorphine‐induced antinociception. Subcutaneous administration of buprenorphine, morphine or fentanyl induced antinociception in the warm‐water (48¡ãC) tail‐dip/flick test in mice in a dose‐related manner. The antinociception induced by all three agonists was attenuated by intrathecal (i.t.) administration of either pertussis toxin (PTX) (1 mg, 48h) or the opioid receptor antagonist naloxone (20 mg). However, intracerebroventricular (i.c.v.) PTX or naloxone administered attenuated only morphine‐ and fentanyl‐induced antinociception. Pretreatment with Gz antisense (14.6 mg, 24 h) i.t. had no effect on any agonist‐induced antinociception. However, pretreatment with Gz antisense (but not control) i.c.v. inhibited buprenorphine‐induced, but not morphine‐ or fentanyl‐induced antinociception. These results reveal that a PTX‐insensitive, Gz transduction pathway plays an important role in buprenorphine‐induced supraspinal antinociception distinct from, or to a greater degree than, morphine or fentanyl. This work was supported by Grünenthal GmbH (Germany).