PMID:10908631

Citation	Joshi, SK, Su, X, Porreca, F and Gebhart, GF (2000) kappa -opioid receptor agonists modulate visceral nociception at a novel, peripheral site of action. J. Neurosci. 20:5874-9
Abstract	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.
Links	PubMed
Keywords	Acetamides/pharmacology; Analgesics, Opioid/pharmacology; Animals; Colon/innervation; Disinfectants; Electrophysiology; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology; Formaldehyde; Ganglia, Spinal/chemistry; Ganglia, Spinal/physiology; Male; Nociceptors/physiology; Oligonucleotides, Antisense/pharmacology; Oligopeptides/pharmacology; Pain/chemically induced; Pain/physiopathology; Physical Stimulation; Pyrrolidines/pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa/agonists; Receptors, Opioid, kappa/analysis; Receptors, Opioid, kappa/genetics; Rectum/innervation; Visceral Afferents/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:OPRM	involved_in	GO:0051930: regulation of sensory perception of pain	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
RAT:OPRK	involved_in	GO:0051930: regulation of sensory perception of pain	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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