Decreased response to GABA-B agonists in longitudinal smooth muscle-myenteric plexus preparations from morphine-tolerant guinea-pigs

S. Luzzi, S. Franchi-Micheli, M. Ciuffi, Ann Maria Gori, Grazia Gentilini, Lucilla Zilletti

Research output: Contribution to journalArticlepeer-review

Abstract

Summaryo1)Responsiveness of guinea-pig ileal longitudinal smooth muscie-myenteric plexus preparations to drugs activating GABA-B receptors was studied in morphine-tolerant animals. For this purpose morphine pellets (75 mg each) were implanted subcutaneously in guinea-pigs and experiments were performed three days later in electrically-stimulated ileal strips.2)Activation of GABA-B receptors with GABA (10-6-10-3 M) or (-)-baclofen (10-6-10-3 M) caused a dose-related inhibition of twitch response that was about 80% lower in preparations from morphine-tolerant animals than in controls. This was found both in preparations maintained in the presence of morphine (10-6 M) and in morphine-free Krebs. The effect was evident also in ileal preparations from morphine-tolerant animals in which a withdrawal syndrome was induced by the administration of naloxone before sacrifice.3)The phenomenon was specific since the dose-response curve of the adenosine-inhibitory effect was comparable in preparations from tolerant animals and controls.4)The hyporesponsiveness to GABA-B receptor activation began 12 h after pellet implantation and was maximal on the third day.5)It is concluded that during tolerance to and withdrawal from morphine there is a hyporesponsiveness of GABA-B receptors in "in vitro" guinea-pig ileal longitudinal muscle-myenteric plexus preparations.

Original languageEnglish
Pages (from-to)773-783
Number of pages11
JournalPharmacological Research Communications
Volume20
Issue number9
DOIs
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Pharmacology

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