Naloxone-insensitive Inhibitory and Excitatory Effects of Opioid Agonists in the Rat Isolated Uterus

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Abstract
Morphine (3 × 10−6−10−3 M) produced a concentration-dependent inhibition of both spontaneous rhythmic contractions and tonic contraction induced by potassium chloride (KCl) (50 mM) in rat isolated uterus. Uteri at the metoestrus phase were the most sensitive to the inhibitory effect of morphine. Morphine-induced relaxation was characterized by a post-wash tonic contraction. The μ-specific opioid agonist, D-alaglymepheglycol (DAGO) (4 × 10−8−1·2 × 10−5 M) did not affect spontaneous rhythmic contraction but produced a partial inhibition of the KCl depolarized uterus. There was no post-wash contraction following DAGO. In contrast to the inhibition produced by both morphine and DAGO, methionine enkephalin (8 × 10−7−2·4 × 10−5 M) produced a concentration-dependent contraction of the KCl depolarized uterus. Naloxone up to 100 μM, propranolol (10 μM), flurbiprofen (50 μM) and metiamide (10 μM) did not affect either the relaxation produced by morphine and DAGO or the contraction produced by methionine enkephalin. The results showed that the opioid agonists may have non-receptor mediated direct effects on the rat uterus.