+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn

+ Translate
+ Recently Requested

The kappa opioid agonist U-50,488H antagonizes respiratory effects of mu opioid receptor agonists in conscious rats



The kappa opioid agonist U-50,488H antagonizes respiratory effects of mu opioid receptor agonists in conscious rats



Journal of Pharmacology and Experimental Therapeutics 264(2): 631-637



The interactive effects of mu and kappa opioid receptor agonists on respiratory function were investigated following their i.c.v. injection into conscious rats. The highly selective mu receptor agonist (D-Ala-2,N-Methyl-Phe-4,Gly-ol) enkephalin (DAMGO; 1.2-10 nmol) and the relatively selective mu agonist morphine (20 and 30 nmol) significantly decreased arterial pH and PO-2, and increased arterial PCO-2 and blood pressure. Morphine and a low dose of DAMGO (1.2 nmol) also significantly elevated respiratory rate. Heart rate was decreased by DAMGO and, depending upon dose, was either decreased (20 nmol) or increased (30 nmol) by morphine. The selective kappa opioid agonist U-50,488H (200 nmol i.c.v.), which by itself had no significant effect on either respiration or cardiovascular function, dose-dependently antagonized the acidotic, hypoxemic and hypercapnic effects of both DAMGO (2.5 nmol) and morphine (30 nmol). Furthermore, these mu antagonistic properties of U-50,488H were blocked completely after pretreatment with 25 nmol of the highly selective kappa opioid antagonist norbinaltorphimine. These results indicate that the antagonism of mu opioid respiratory depressant effects by U-50,488H is kappa opioid receptor mediated.

(PDF emailed within 1 workday: $29.90)

Accession: 009534135

Download citation: RISBibTeXText

PMID: 8382278


Related references

Studies on drug dependence Effects of a selective kappa-opioid agonist, U-50, 488H, an delta-opioid agonists-induced place preference. Japanese Journal of Pharmacology 64(SUPPL 1): 221P, 1994

Differential effects of micro-opioid, delta-opioid and kappa-opioid receptor agonists on dopamine receptor agonist-induced climbing behavior in mice. Behavioural Pharmacology 17(8): 691-701, 2006

Effects of U-50,488H on isolated atria from rats chronically treated with the kappa-opioid agonist, U-50,488H. Journal of Autonomic Pharmacology 18(6): 371-375, 1999

Effect of chronic administration of naltrexone on brain mu- and kappa-opioid receptors and responses to U-50,488H, a kappa-opioid receptor agonist in the mouse. FASEB Journal 9(3): A102, 1995

Generalization of NMDA-receptor antagonists to the discriminative stimulus effects of kappa-opioid receptor agonists U-50,488H, but not TRK-820 in rats. Journal of Pharmacological Sciences 100(2): 157-161, 2006

Antitussive effects of two specific kappa-opioid agonists, U-50,488H and U-62,066E, in rats. European Journal of Pharmacology 187(2): 281-286, 1990

Effects of naloxone, morphine and kappa-opioid receptor agonists on hypoxia/hypoglycemia-induced reduction of 2-deoxyglucose uptake in hippocampal slices from U-50,488H-tolerant rats. Neuroscience Letters 182(2): 155-158, 1994

Contralateral, ipsilateral and bilateral treatments with the kappa-opioid receptor agonist U-50,488H in mononeuropathic rats. European Journal of Pharmacology 494(2-3): 139-146, 2004

Effects of a selective kappa-opioid agonist, U-50,488H, on morphine dependence in rats. European Journal of Pharmacology 170(1-2): 47-51, 1989

Opioid induced respiratory depression antagonized by opioid agonist MR-2034 but not by U-50,488H in freely moving rats. Regulatory Peptides 54(1): 215-216, 1994

Effects of the kappa-opioid receptor agonist U50,488H on volitional ethanol intake in the Lewis rat. Society for Neuroscience Abstracts 25(1-2): 1081, 1999

Kappa-opioid receptor agonist U50,488H modulates cocaine and morphine self-administration in drug-naive rats and mice. European Journal of Pharmacology 321(3): 265-271, 1997

Effects of U-50,488H, a kappa-opioid receptor agonist, on the learned helplessness model of depression in mice. Journal of Neural Transmission 109(9): 1221-1225, 2002

Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A. Naunyn-Schmiedeberg's Archives of Pharmacology 379(3): 263-270, 2008

Modification of the binding of [3H]MK-801 to brain regions and spinal cord of rats treated chronically with U-50,488H, a kappa-opioid receptor agonist. Brain Research 749(2): 347-350, 1997