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.
Ozaki
M
M
Department of Toxicology, Niigata College of Pharmacy, Niigata 950-2076, Japan.
Masuda
Y
Y
Kishioka
S
S
Yamamoto
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000315:Adrenalectomy; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D004723:Endorphins / Q000378:metabolism*; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000097:blood; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D004723:Endorphins; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; D000109:Acetylcholine; D006854:Hydrocortisone