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Biomedical subjects

E L Way

Publications and source records attributed to E L Way.

At least 73 records · Page 4Linked to original sources
PubMed1980

Methionine-enkephalin antagonism and endorphin potentiation of narcotic-induced analgesia.

Intracerebroventricular (i.c.v.) administration of subanalgesic doses of beta- and leucine-endorphin in mice 15 min before subcutaneous morphine injection, significantly enhanced the analgesic effects of the morphine as measured by the tail-flick assay. A similar effect was seen with levorphanol analgesia but not enhancement of leucine- or methionine-enkephalin analgesia by beta-endorphin was observed. The same doses of the endorphins did not affect the development of single-dose morphine tolerance and dependence. Leucine-enkephalin failed to affect morphine analgesia, tolerance or dependence development, while low doses of methionine-enkephalin administered i.c.v. were observed to have an antagonistic effect on morphine analgesia without affecting tolerance or dependence development. Neither endephalin had any effect on beta-endorphin analgesia.

Animals↗
PubMed1980

Effect of a calcium chelator on morphine tolerance development.

To assess the effects of calcium ion chelation on narcotic tolerance development, adult Sprague-Dawley rats were implanted with i.c.v. cannulae connected to osmotic minipumps for continuous infusions of saline or EGTA (2 mumol/24 h) during chronic morphinization by s.c. pellet implantation. Additional rats receiving the same morphine pellet treatment but without minipumps served as non-surgical controls. After 64 h the minipumps and pellets were removed and narcotic tolerance was assessed by the tail-flick technique. A positive analgetic response to an 8.50 mg/kg s.c. dose of morphine sulfate was noted in 6/12 no-minipump controls and 4/9 saline-infused controls. In placebo-treated rats caused no alteration of either baseline tail-flick latencies or in analgetic responsiveness to lower doses of morphine. It is concluded that the enhancement of morphine tolerance by EGTA (a calcium-specific chelator) results from a facilitation of certain adaptive changes of calcium ion disposition that are related to the neurochemical mechanisms of narcotic tolerance and dependence development.

Analgesics↗
PubMed1980

Tolerance to methadone lethality and microsomal enzyme induction in mice tolerant to and dependent on morphine.

In an attempt to explain a loss of cross-tolerance between morphine and methadone and an increased tolerance to methadone lethality in morphine-dependent mice administered methadone orally for six days, the possibility that methadone was stimulating its own metabolism was investigated. It was found that methadone did enhance its own metabolism two-fold. This increase in activity correlated with the development of tolerance to the lethal effects of methadone as measured by an elevation of the oral methadone LD50. Furthermore, SKF-525A, a potent microsomal inhibitor, abolished this tolerance. The intracerbroventricular methadone LD50 was not altered by six days administration of oral methadone, suggesting that the tolerance observed was dispositional in nature.

Animals↗
PubMed1980

Hyperalgesic effects of divalent cations and antinociceptive effects of a calcium chelator in naive and morphine-dependent mice.

Using a modified tail-flick procedure we have found a highly significant hyperalgesic response in narcotic dependent mice peaking 12 hr following the removal of chronically implanted morphine pellets. Withdrawal-induced hyperalgesia correlated well with other signs of opiate withdrawal behavior. Intracerebroventricular injections of CaCl2, MnCl2 further enhanced the hyperalgesic response in morphine-dependent mice; morphine-dependent mice were more than twice as sensitive to calcium-induced hyperalgesia as placebo-treated controls. On the other hand, i.c.v. injections of the calcium-specific chelator EGTA produced highly significant, dose-dependent antinociceptive responses in both morphine-dependent and control mice, but morphine dependent mice were only half as sensitive to EGTA-induced analgesia as controls. Withdrawal hyperalgesia and EGTA analgesia may be directly related to changes in brain localization of calcium that have been reported previously; it is concluded that morphine and EGTA-induced analgesia may be associated with a calcium depleted state within a relatively small calcium pool of the nerve cell and that opiate withdrawal hyperalgesia is a sensitive measure of narcotic dependency that is likely associated with an increased Ca++ content in the same region.

Animals↗
PubMed1979

Effect of beta-endorphin on calcium uptake in the brain.

The uptake of 45Ca2+ by nerve-ending fractions from brains of mice was inhibited in vitro by 10(-9)M concentrations of beta-endorphin and in mice injected intraventricularly with 7 picomoles of beta-endorphin. That the effect was a specific opiate agonist response of beta-endorphin was demonstrated by use of the opiate antagonist, naloxone, which reversed the action. A role for beta-endorphin in the regulation of calcium flux and neurotransmitter release should be considered.

Animals↗