Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

01 August 2010

Long-term adaptation to high doses of morphine causes desensitization of micro-OR- and delta-OR-stimulated G-protein response in forebrain cortex but does not decrease the amount of G-protein alpha subunits

Lenka BourovaBCDE, Miroslava VosahlikovaBD, Dmytro KaganB, Katerina DlouhaBD, Jiri NovotnyBF, Petr SvobodaACDEFG

Med Sci Monit 2010; 16(8): BR260-270 :: ID: 881099

Abstract

Background: The functional activity of trimeric guanine-nucleotide-binding proteins (G-proteins) represents an essential step in linking and regulation of the opioid receptor (micro-,delta- and kappa-OR)-initiated signaling pathways. Theoretical basis and/or molecular mechanism(s) of opioid tolerance and addiction proceeding in the central nervous system were not studied in the forebrain cortex of mammals with respect to quantitative analysis of opioid-stimulated trimeric G-protein activity.
Material/Methods: G-protein activity was measured in PercollR-purified plasma membranes (PM) isolated from the frontal brain cortex of control and morphine-treated rats by both high-affinity [32P]GTPase and [35S]GTPgammaS binding assays. Exposition to morphine was performed by intra-muscular application of this drug. Control animals were injected with sterile PBS.
Results: Both micro-OR (DAMGO)- and delta-OR (DADLE)-responses were clearly desensitized in PM isolated from morphine-treated rats; kappa-OR (U-69593)- and baclofen (GABAB-R)-stimulated [35S]GTPgammaS binding was unchanged, indicating the specificity of the morphine effect. Under such conditions, the amount of G-protein alpha subunits was unchanged. The order of efficacy DADLE>DAMGO>U-69593 was the same in control and morphine-treated PM. Behavioral tests indicated that morphine-treated animals were fully drug-dependent and developed tolerance to subsequent drug addition.
Conclusions: Prolonged exposure of rats to high doses of morphine results in decrease of the over-all output of OR-stimulated G-protein activity in the forebrain cortex but does not decrease the amount of these regulatory proteins. These data support the view that the mechanism of the long-term adaptation to high doses of morphine is primarily based on desensitization of OR-response preferentially oriented to micro-OR and delta-OR.

Keywords: Morphine - pharmacology, Guanosine Diphosphate - metabolism, Guanosine 5'-O-(3-Thiotriphosphate) - metabolism, GTP-Binding Protein alpha Subunits - metabolism, Enkephalin, Ala(2)-MePhe(4)-Gly(5)- - pharmacology, Drug Tolerance, Dose-Response Relationship, Drug, Cerebral Cortex - metabolism, Cell Membrane - enzymology, Behavior, Animal - drug effects, Baclofen - pharmacology, Adaptation, Physiological - drug effects, Rats, Wistar, Receptors, Opioid, delta - metabolism, Receptors, Opioid, mu - metabolism, Substance Withdrawal Syndrome - physiopathology, Time Factors

Add Comment 0 Comments

Editorial

01 April 2024 : Editorial  

Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug Resistance

Dinah V. Parums

DOI: 10.12659/MSM.944600

Med Sci Monit 2024; 30:e944600

0:00

In Press

06 Mar 2024 : Clinical Research  

Prevalence and Variation of Medical Comorbidities in Oral Surgery Patients: A Retrospective Study at Jazan ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943884  

08 Mar 2024 : Clinical Research  

Evaluation of Foot Structure in Preschool Children Based on Body Mass

Med Sci Monit In Press; DOI: 10.12659/MSM.943765  

15 Apr 2024 : Laboratory Research  

The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in Osteoarthritis

Med Sci Monit In Press; DOI: 10.12659/MSM.943738  

07 Mar 2024 : Clinical Research  

Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...

Med Sci Monit In Press; DOI: 10.12659/MSM.943468  

Most Viewed Current Articles

17 Jan 2024 : Review article  

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research  

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750