Tags

Type your tag names separated by a space and hit enter

In vivo injection of antisense oligodeoxynucleotides to G alpha subunits and supraspinal analgesia evoked by mu and delta opioid agonists.
J Pharmacol Exp Ther. 1995 Dec; 275(3):1590-6.JP

Abstract

For 5 consecutive days repeated intracerebroventricular (i.c.v.) administration of antisense oligodeoxynucleotides (ODNs) to G alpha subunit mRNAs was used to impair the function of mouse Gi1, Gi2, Gi3 and Gx/z regulatory proteins. Decreases of 20 to 60% on the G alpha-like immunoreactivity could be observed in neural structures of mouse brain, an effect that was not produced by a random-sequence ODN used as a control. The ODN to Gi1 alpha subunits lacked effect on opioid-evoked analgesia. In mice injected with the ODN to Gi2 alpha subunits the antinociceptive activity of all the opioids studied appeared greatly impaired. The ODN to Gi3 alpha subunits reduced the effects of the selective agonists of delta opioid receptors, [D-Pen2,5]-enkephalin and [D-Ala2]deltorphin II. Conversely, the analgesia evoked by opioids binding mu opioid receptors, [D-Ala2, N-MePhe4,Gly-ol5]enkephalin and morphine, appeared consistently and significantly attenuated in mice injected with the ODN to Gx/z alpha. The effect of the neuropeptide beta-endorphine-(1-31) agonist at mu and delta receptors was also reduced by ODNs to Gi3 alpha or Gx/z alpha subunits. l.c.v. injection of antibodies directed to these G alpha subunits antagonized opioid-induced analgesia with a pattern similar to that observed for the ODNs. Thus, the mu and delta opiod receptors regulate different classes of G transducer proteins to mediate the analgesic effect of agonists. The in vivo antisense strategy and the use of specific antibodies to G alpha subunits gave comparable results, indicating that in the neural tissue the mRNAs and the G alpha subunits can be accessed by the corresponding ODNs and IgGs.

Authors+Show Affiliations

Instituto de Neurobiología Santiago Ramón y Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8531133

Citation

Sánchez-Blázquez, P, et al. "In Vivo Injection of Antisense Oligodeoxynucleotides to G Alpha Subunits and Supraspinal Analgesia Evoked By Mu and Delta Opioid Agonists." The Journal of Pharmacology and Experimental Therapeutics, vol. 275, no. 3, 1995, pp. 1590-6.
Sánchez-Blázquez P, García-España A, Garzón J. In vivo injection of antisense oligodeoxynucleotides to G alpha subunits and supraspinal analgesia evoked by mu and delta opioid agonists. J Pharmacol Exp Ther. 1995;275(3):1590-6.
Sánchez-Blázquez, P., García-España, A., & Garzón, J. (1995). In vivo injection of antisense oligodeoxynucleotides to G alpha subunits and supraspinal analgesia evoked by mu and delta opioid agonists. The Journal of Pharmacology and Experimental Therapeutics, 275(3), 1590-6.
Sánchez-Blázquez P, García-España A, Garzón J. In Vivo Injection of Antisense Oligodeoxynucleotides to G Alpha Subunits and Supraspinal Analgesia Evoked By Mu and Delta Opioid Agonists. J Pharmacol Exp Ther. 1995;275(3):1590-6. PubMed PMID: 8531133.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo injection of antisense oligodeoxynucleotides to G alpha subunits and supraspinal analgesia evoked by mu and delta opioid agonists. AU - Sánchez-Blázquez,P, AU - García-España,A, AU - Garzón,J, PY - 1995/12/1/pubmed PY - 1995/12/1/medline PY - 1995/12/1/entrez SP - 1590 EP - 6 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 275 IS - 3 N2 - For 5 consecutive days repeated intracerebroventricular (i.c.v.) administration of antisense oligodeoxynucleotides (ODNs) to G alpha subunit mRNAs was used to impair the function of mouse Gi1, Gi2, Gi3 and Gx/z regulatory proteins. Decreases of 20 to 60% on the G alpha-like immunoreactivity could be observed in neural structures of mouse brain, an effect that was not produced by a random-sequence ODN used as a control. The ODN to Gi1 alpha subunits lacked effect on opioid-evoked analgesia. In mice injected with the ODN to Gi2 alpha subunits the antinociceptive activity of all the opioids studied appeared greatly impaired. The ODN to Gi3 alpha subunits reduced the effects of the selective agonists of delta opioid receptors, [D-Pen2,5]-enkephalin and [D-Ala2]deltorphin II. Conversely, the analgesia evoked by opioids binding mu opioid receptors, [D-Ala2, N-MePhe4,Gly-ol5]enkephalin and morphine, appeared consistently and significantly attenuated in mice injected with the ODN to Gx/z alpha. The effect of the neuropeptide beta-endorphine-(1-31) agonist at mu and delta receptors was also reduced by ODNs to Gi3 alpha or Gx/z alpha subunits. l.c.v. injection of antibodies directed to these G alpha subunits antagonized opioid-induced analgesia with a pattern similar to that observed for the ODNs. Thus, the mu and delta opiod receptors regulate different classes of G transducer proteins to mediate the analgesic effect of agonists. The in vivo antisense strategy and the use of specific antibodies to G alpha subunits gave comparable results, indicating that in the neural tissue the mRNAs and the G alpha subunits can be accessed by the corresponding ODNs and IgGs. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8531133/In_vivo_injection_of_antisense_oligodeoxynucleotides_to_G_alpha_subunits_and_supraspinal_analgesia_evoked_by_mu_and_delta_opioid_agonists_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8531133 DB - PRIME DP - Unbound Medicine ER -