Morphine and Naloxone: Effects on β-Endorphin Immunoreactivity in Canine Plasma and Secretions from Rat Pituitaries*

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Abstract
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 < 0.05) increase in plasma β-endorphin immunoreactivity (βEI) 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 βEI, morphine (4–6 μg) failed to affect βEI release. Naloxone, surprisingly, also caused a significant (P < 0.025) release of βEI. After naloxone, βEI 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 β-lipotropin compared to β-endorphin. To determine the site of stimulation of βEI 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 βEI from the pituitaries. In a second set of experiments we compared the effect on βEI release of hypothalamic median eminence extract alone or with morphine. Hypothalamic median eminence extract at two concentrations produced significant release of βEI, 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.