The effect of morphine pretreatment on the sensitivity of mouse and guinea-pig ileum to acetylcholine and to morphine

Abstract

Guinea‐pigs and mice were subjected to morphine pretreatment for at least 14 days culminating in subcutaneous injections of 1 g/kg daily in 2 divided doses. In mice, tolerance to the effects of morphine on gastrointestinal propulsion had developed by the end of the pretreatment course. The sensitivity to acetylcholine of the ilia from pretreated animals and the effects of morphine on transmural stimulation were compared with the ilia from normal animals. Ilia from pretreated guinea‐pigs were marginally more sensitive to frequency of stimulation but significantly less sensitive to the depressant effect of morphine than ilia from normal animals. There was no significant difference in the sensitivity to acetylcholine. There was a highly significant decrease in sensitivity to morphine of ilia from pretreated mice, but this also was not associated with any alteration in sensitivity to acetylcholine. It is concluded that on the isolated ileum preparation the development of tolerance to morphine is not associated with an increased sensitivity to the transmitter whose release morphine inhibits.

Morphine‐tolerant longitudinal muscle strip from guinea‐pig ileum

“…As shown in Fig. 6, the responses to ACh (0-05-24 nM) were about the same in controls and in strips prepared on the 3rd, 6th and 9th day after pellet implantation, as also shown by Haycock & Rees (1972). Effects of adrenaline, isoprenaline and dopamine on the responses of electrically stimulated myenteric plexus-longitudinal muscle preparation Adrenaline, isoprenaline and dopamine inhibited the electrically induced twitch (Figures 7-9).…”

Opiate Binding and Effect in Ileum Preparations From Normal and Morphine Pretreated Guinea‐pigs

“…The receptors mediating this effect are similar to opiate receptors in the central nervous system with respect to (i) the relative potencies of opiate agonists (Paton, 1957;Cox & Weinstock, 1966;Kosterlitz, Lord & Watt, 1972), (ii) antagonism by appropriately substituted opiate drugs (Cox & Weinstock, 1966;Gyang & Kosterlitz, 1966;Kosterlitz & Watt, 1968) and (iii) stereospecificity, both for agonists and antagonists (Cox & Weinstock, 1966). Pretreatment of the guinea-pig with morphine results in a reduced sensitivity to opiates of the subsequently isolated ileum (Haycock & Rees, 1973;Goldstein & Schulz, 1973;Ward & Takemori, 1976). Recently, a high affinity stereospecific component of the binding of opiate drugs to homogenates of longitudinal muscle-myenteric plexus preparations from guinea-pig ileum has been shown to possess the expected characteristics of opiate receptor binding (Terenius, 1973;Creese & Snyder, 1975).…”