Morphine and naloxone: effects on beta-endorphin immunoreactivity in canine plasma and secretions from rat pituitaries.
Morphine and naloxone were administered to five dogs to assess their effects on endogenous opioid release. Morphine (3 mg/20 kg) produced a significant (P less than 0.05) increase in plasma beta-endorphin immunoreactivity(beta EI) compared to saline control. The peak stimulation [19.2 +/- 4.97 baseline to 48.1 +/- 6.82 (SEM) pg/ml] occurred at +10 min and rapidly returned to preinjection levels at +60. At a dose 10 times equipotent to circulating basal beta EI, morphine (4-6 micrograms) failed to affect beta EI release. Naloxone, surprisingly, also caused a significant (P less than 0.025) release of beta EI. After naloxone, beta EI rose from a preinjection baseline of 36.4 +/- 5.82 pg/ml to a peak of 172 +/- 44.1 pg/ml at 45 min post injection. Naloxone pretreatment also obscured the effect of subsequently injected morphine (3 mg/20 kg). In three naloxone-treated dogs, gel chromatography of pooled basal and peak plasma revealed a preponderance of beta-lipotropin compared to beta-endorphin. To determine the site of stimulation of beta EI by opiates and opioids, a series of rat anterior pituitary incubations were performed. Neither morphine (10(-6) M) nor D-Ala2-methionine enkephalinamide (10(-6) M) nor naloxone (10(-6) M) had an effect significantly different from control medium on the release of beta EI from the pituitaries. In a second set of experiments we compared the effect on beta EI release of hypothalamic median eminence extract alone or with morphine. Hypothalamic median eminence extract at two concentrations produced significant release of beta EI, which was unaffected by the addition of morphine. These results suggest that stimulation of release of endogenous opioid peptides by opiates occurs at a suprapituitary level.
D000818:Animals; D004723:Endorphins / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D001615:beta-Endorphin; D008083:beta-Lipotropin / Q000097:blood
D004723:Endorphins; D009270:Naloxone; D001615:beta-Endorphin; D009020:Morphine; D008083:beta-Lipotropin