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Dissociation of opioid antinociception and central gastrointestinal propulsion in the mouse: studies with naloxonazine.
J Pharmacol Exp Ther. 1988 Apr; 245(1):238-43.JP

Abstract

The effect of pretreatment with naloxonazine on opioid-mediated antinociception against a thermal stimulus (55 degrees C warm-water tail-flick test) and inhibition of gastrointestinal transit at supraspinal and spinal levels was studied in unanesthetized mice. The mu-selective agonist [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAGO), the delta-selective agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) and the reference mu-acting agonist morphine, all produced antinociception after either i.c.v. or intrathecal(ly) (i.t.) administration. Morphine and DAGO, but not DPDPE, inhibited gastrointestinal transit after i.c.v. administration, whereas all three agonists slowed gut propulsion when given i.t. A single s.c. naloxonazine pretreatment, 35 mg/kg given 24 hr earlier, failed to displace the dose-response line for i.c.v. DPDPE antinociception but produced a marked rightward displacement of the i.c.v. morphine and DAGO dose-response lines for antinociception. In contrast, naloxonazine (35 mg/kg) pretreatment did not alter the antinociceptive effects of i.t. morphine, DAGO or DPDPE. The effects of naloxonazine pretreatment on inhibition of gut propulsion were the converse of those observed for antinociception at supraspinal and spinal sites; naloxonazine had no effect on the antitransit properties of i.c.v. morphine and DAGO but inhibited the antitransit properties of all three agonists when they were given i.t. These results support the view that opioids may produce their supraspinal antitransit effects at a receptor different from that mediating antinociception; morphine and DAGO mediate their antitransit effects at a naloxonazine-insensitive site, whereas their antinociceptive effects are produced at the naloxonazine-sensitive receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2834537

Citation

Heyman, J S., et al. "Dissociation of Opioid Antinociception and Central Gastrointestinal Propulsion in the Mouse: Studies With Naloxonazine." The Journal of Pharmacology and Experimental Therapeutics, vol. 245, no. 1, 1988, pp. 238-43.
Heyman JS, Williams CL, Burks TF, et al. Dissociation of opioid antinociception and central gastrointestinal propulsion in the mouse: studies with naloxonazine. J Pharmacol Exp Ther. 1988;245(1):238-43.
Heyman, J. S., Williams, C. L., Burks, T. F., Mosberg, H. I., & Porreca, F. (1988). Dissociation of opioid antinociception and central gastrointestinal propulsion in the mouse: studies with naloxonazine. The Journal of Pharmacology and Experimental Therapeutics, 245(1), 238-43.
Heyman JS, et al. Dissociation of Opioid Antinociception and Central Gastrointestinal Propulsion in the Mouse: Studies With Naloxonazine. J Pharmacol Exp Ther. 1988;245(1):238-43. PubMed PMID: 2834537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dissociation of opioid antinociception and central gastrointestinal propulsion in the mouse: studies with naloxonazine. AU - Heyman,J S, AU - Williams,C L, AU - Burks,T F, AU - Mosberg,H I, AU - Porreca,F, PY - 1988/4/1/pubmed PY - 1988/4/1/medline PY - 1988/4/1/entrez SP - 238 EP - 43 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 245 IS - 1 N2 - The effect of pretreatment with naloxonazine on opioid-mediated antinociception against a thermal stimulus (55 degrees C warm-water tail-flick test) and inhibition of gastrointestinal transit at supraspinal and spinal levels was studied in unanesthetized mice. The mu-selective agonist [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAGO), the delta-selective agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) and the reference mu-acting agonist morphine, all produced antinociception after either i.c.v. or intrathecal(ly) (i.t.) administration. Morphine and DAGO, but not DPDPE, inhibited gastrointestinal transit after i.c.v. administration, whereas all three agonists slowed gut propulsion when given i.t. A single s.c. naloxonazine pretreatment, 35 mg/kg given 24 hr earlier, failed to displace the dose-response line for i.c.v. DPDPE antinociception but produced a marked rightward displacement of the i.c.v. morphine and DAGO dose-response lines for antinociception. In contrast, naloxonazine (35 mg/kg) pretreatment did not alter the antinociceptive effects of i.t. morphine, DAGO or DPDPE. The effects of naloxonazine pretreatment on inhibition of gut propulsion were the converse of those observed for antinociception at supraspinal and spinal sites; naloxonazine had no effect on the antitransit properties of i.c.v. morphine and DAGO but inhibited the antitransit properties of all three agonists when they were given i.t. These results support the view that opioids may produce their supraspinal antitransit effects at a receptor different from that mediating antinociception; morphine and DAGO mediate their antitransit effects at a naloxonazine-insensitive site, whereas their antinociceptive effects are produced at the naloxonazine-sensitive receptor.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2834537/Dissociation_of_opioid_antinociception_and_central_gastrointestinal_propulsion_in_the_mouse:_studies_with_naloxonazine_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2834537 DB - PRIME DP - Unbound Medicine ER -