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 i n guinea-pig isolated myenteric plexus-longitudinal muscle (MPLM) were inve stigated. 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 mug 100 ml(-1); adrenalectomized: 20.0 +/-3.6 mug 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 intens ity), caused by a low concentration of morphine (5 x 10(-9)-5 x 10(-7) M) w as not affected, but at high concentration (10(-6)-10(-5) M) there was an u pward shift in the adrenalectomized group compared with the sham-operated c ontrol, although the basal twitch contraction was not changed by adrenalect omy. 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 intens ity, for 1 min) was inhibited in the adrenalectomized group compared with t he 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 adre nalectomy. 7 These results suggested a possible mechanism for the increase in sensitiv ity 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.