Adrenalectomy-induced potentiation of morphine action in guinea-pig ileum: possible decrease in the release of endogenous opioids from opioidergic neurones.

1. The effects of adrenalectomy on exogenous and endogenous opioid actions in guinea-pig isolated myenteric plexus-longitudinal muscle (MPLM) were investigated. 2. A decrease in serum cortisol level to about 37% of the level in the sham-operated group was obtained in adrenalectomized animals (sham: 53.5 +/- 7.2 microg 100 ml(-1); adrenalectomized: 20.0 +/- 3.6 microg 100 ml(-1)). 3. The concentration-response curve of twitch inhibition, which was induced by electrical field stimulation (0.1 Hz, 0.5 ms pulse width, maximum intensity), caused by a low concentration of morphine (5 x 10(-9)-5 x 10(-7) M) was not affected, but at high concentration (10(-6)-10(-5) M) there was an upward shift in the adrenalectomized group compared with the sham-operated control, although the basal twitch contraction was not changed by adrenalectomy. 4. The twitch inhibition induced by a high concentration of morphine (10(-6) M) in the adrenalectomized group was antagonized to the same level as that in sham-operated controls by naloxone (NLX) (3 x 10(-7) M). 5 Post-tetanic twitch inhibition, an indicator of endogenous opioid release, induced by tetanic stimulation (10 Hz, 0.5 ms pulse width, maximum intensity, for 1 min) was inhibited in the adrenalectomized group compared with the sham-operated controls. The antagonism of inhibition in both groups was equivalent to that exerted by NLX (10(-7) M). 6. Acetylcholine-evoked contraction of the muscle was not influenced by adrenalectomy. 7. These results suggested a possible mechanism for the increase in sensitivity of the opioid receptors to morphine by adrenalectomy, resulting from a decrease in the release of endogenous opioids from the opioidergic neurones in the ileum.