The possible role of intracellular receptors in the expression of narcotic antagonist precipitated abstinence.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A K Killian.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Antimorphine globulin was used to study the mechanism by which naloxone produces a contracture in ileal strips removed from morphine pellet-implanted guinea pigs. Although the antibodies effectively reversed the depressant actions of morphine on electrically stimulated contractions in both naive and tolerant tissues, neither monkey antimorphine (Kd = 1.43 x 10(-7)M) nor goat antimorphine (Kd = 1.36 x 10(-9)M) were able to elicit a naloxone-like contracture. The rate of attenuation of tissue sensitivity to naloxone was measured and no changes were observed after incubation in the presence of monkey antimorphine globulin. High-affinity goat antimorphine globulin, however, was able to accelerate the rate of attenuation of tissue sensitivity to naloxone. The naloxone contracture was accompanied by release of material reactive with morphine antiserum in a radioimmunoassay. The quantities of material were in excess of what could be bound by opiate receptors present in the tissue. Possible mechanisms of naloxone sensitivity observed in the isolated ileum are discussed.
The effects of repeated administration of naloxone on heroin and cocaine self-administration in non-dependent rhesus monkeys were investigated. Animals lever pressing for intravenous heroin (6 micron/kg) and cocaine (100 or 200 micron/kg) were treated for 7--10 days with naloxone at a fixed dose prior to each session. Low pretreatment doses of naloxone increased rate of responding maintained by herion. The pattern of responding over the 10-day period of treatment with the higher doses of naloxone was similar to that observed when saline was substituted for heroin. Naloxone was without effect on responding maintained by injections of cocaine.