RGD Reference Report - kappa -opioid receptor agonists modulate visceral nociception at a novel, peripheral site of action. - Rat Genome Database

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kappa -opioid receptor agonists modulate visceral nociception at a novel, peripheral site of action.

Authors: Joshi, SK  Su, X  Porreca, F  Gebhart, GF 
Citation: Joshi SK, etal., J Neurosci. 2000 Aug 1;20(15):5874-9.
RGD ID: 9831416
Pubmed: PMID:10908631   (View Abstract at PubMed)
PMCID: PMC6772560   (View Article at PubMed Central)

kappa-opioid receptor agonists (kappa-ORAs) have been shown to modulate visceral nociception through an interaction with a peripheral, possibly novel, kappa-opioid-like receptor. We used in the present experiments an antisense strategy to further explore the hypothesis that kappa-ORA effects in the colon are produced at a site different from the cloned kappa-opioid receptor (KOR). An antisense oligodeoxynucleotide (ODN) to the cloned rat KOR was administered intrathecally (12.5 microg, twice daily for 4 d) to specifically knock-down the cloned KOR. Efficacy of the KOR antisense ODN treatment was behaviorally evaluated by assessing the antinociceptive effects of peripherally administered kappa- (EMD 61, 753 and U 69,593), mu- (DAMGO) and delta- (deltorphin) ORAs in the formalin test. Intrathecal antisense, but not mismatch ODN blocked the actions of EMD 61,753 and U 69,593 without affecting the actions of DAMGO or deltorphin; a complete recovery of antinociceptive actions of the kappa-ORA EMD 61,753 was observed 10 d after the termination of antisense ODN treatment. In contrast, the ability of EMD 61,753 to dose-dependently attenuate responses of pelvic nerve afferent fibers to noxious colonic distension was unaffected in the same rats in which the antisense ODN effectively knocked-down the KOR as assessed in the formalin test. Additionally, Western blot analysis demonstrated a significant downregulation of KOR protein in the L4-S1 dorsal root ganglia of antisense, but not mismatch ODN-treated rats. The present results support the existence of a non-kappa-opioid receptor site of action localized in the colon.

Objects referenced in this article
Gene Oprd1 opioid receptor, delta 1 Rattus norvegicus
Gene Oprk1 opioid receptor, kappa 1 Rattus norvegicus
Gene Oprm1 opioid receptor, mu 1 Rattus norvegicus

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