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Biomedical subjects

B M Cox

Publications and source records attributed to B M Cox.

At least 109 records · Page 6Linked to original sources
PubMed1977

Distribution of endorphins (peptides with morphine-like pharmacological activity) in pituitary.

Endorphin was found in the pituitary gland of rat, sheep, pig, cow and man. In bovine pituitary, highest concentrations have been found in that part of the posterior lobe containing the pars intermedia, although endorphin was also present in the pars distalis. Analysis by gel filtration and adsorption chromatography suggested that the major endorphins from rat, pig and cow pituitary were similar, with apparent molecular weights in the range 3000-3500 daltons.

Animals↗
PubMed1977

Opiate receptors.

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Affinity Labels↗
PubMed1977

Opiate binding and effect in ileum preparations from normal and morphine pretreated guinea-pigs.

1 Dose-response curves for normorphine in the absence and presence of naloxone have been obtained from myenteric plexus-longitudinal muscle strip preparations from normal and morphine pretreated guinea-pigs. In addition, the high affinity stereospecific binding of [3H]-etorphine has been measured in homogenates of the same tissue. 2 Higher concentrations of normorphine were required to produce 50% inhibition of the electrically stimulated contractions of strip preparations from morphine pretreated animals. There was also an increase in the slope of linearized dose-response curves in opiate-tolerant preparations. Maximum opiate effect was unchanged, and responses to exogenous acetylcholine were not affected by the pretreatment. 3 There was a slight increase in the apparent equilibrium constant for naloxone after morphine pretreatment. 4 Tolerance to opiate effect was not accompanied by a change in the affinity or number of stereospecific binding sites for [3H]-etorphine. Hill plots of [3H]-etorphine binding in both control and morphine pretreated preparations gave slopes close to unity. 5 Most of these results can be explained by the assumption that in tolerant preparations, a certain fractional opiate receptor occupation threshold must be exceeded before opiate effects become apparent. It is suggested that the tissue adapts toward a threshold equivalent to the mean receptor occupancy attained during the period of opiate drug pretreatment.

Acetylcholine↗
PubMed1976

Further characterization of morphine-like peptides (endorphins) from pituitary.

Pituitary peptides with opioid pharmacologic action (endorphins) can exist in several forms with different basicities and molecular weights from about 3000 to less than 1000 daltons. Partial purification yielded an endorphin at least 4 times more potent than normorphine and 16 times more potent than the endogenous brain pentapeptide methionine enkephalin. It is proposed that pituitary endorphin or a similar peptide in brain may be the precursor of brain enkephalin.

Adrenocorticotropic Hormone↗
PubMed1976

Opioid activity of a peptide, beta-lipotropin-(61-91), derived from beta-lipotropin.

The pituitary peptide beta-lipotropin displays essentially no opoid activity in a preparation of guinea pig ileum or in the opiate receptor binding assay. However, a fragment, beta-lipotropin-(61-91), with the enkephalin sequence (Tyr-Gly-Gly-Phe-Met) at its NH2-terminus, has typical opioid effects in these two assays.

Amino Acid Sequence↗
PubMed1975

The offset of morphine tolerance in rats and mice.

1. In rats and mice made tolerant to morphine by pretreatment with the drug, the shift to the right of the log dose/analgesic response line for in naive animals occurs without significant change in slope provided that sufficient time is allowed for elimination of pretreatment drug. 2. Responsiveness to the analgesic effects of morphine, given together with cycloheximide to prevent reinforcement of tolerance, was measured in rats (paw pressure method) and mice (hot plate method) at intervals during 1-23 days following cessation of a variety of regimens of tolerance-inducing drug treatments. 3. A biphasic pattern of recovery of responsiveness was observed, which was independent of the regimen or the drug (morphine, methadone or diamorphine) used to induce tolerance. Estimates of the rates of the first, fast phase are imprecise but the rate of the second phase of offset, from 4th day after cessation of pretreatment had, in rats, a mean half-time of 13.2 plus or minus 0.53 days-for all pretreatments combined, there being no significant differences between the various pretreatment regimens employed. In mice, similarly, a biphasic recovery of analgesic responsiveness was seen after morphine pretreatment, the mean half-time of the slower phase being 17.4 days. 4. Precipitation of an acute withdrawal syndrome in rats by naloxone HCl given 6 h after the final injection of a tolerance-inducing treatment with morphine did not affect the subsequent rate of recovery from tolerance. 5. During the period following a tolerance-inducing pretreatment with morphine in mice, the rate of attenuation of the naloxone-evoked jumping response was faster than the rate of offset of tolerance.

Analgesics↗
PubMed1970

Inhibition of the development of tolerance to morphine in rats by drugs which inhibit ribonucleic acid or protein synthesis.

1. A study has been made of the effects of a number of drugs which have as a common property the ability to inhibit RNA or protein synthesis, on the development of tolerance to the analgesic effects of morphine, given by intravenous infusion, in rats.2. Measurements were also made of the effects of the drugs on the incorporation of (14)C-lysine into rat brain protein, and (14)C-orotic acid into rat brain RNA.3. Actinomycin D, 6-mercaptopurine and 5-fluorouracil reduced the acquisition of tolerance to morphine at doses which also produced significant inhibition of incorporation of orotic acid into brain RNA. Tolerance development was only affected by 6-mercaptopurine and 5-fluorouracil after intracerebral administration.4. 6-Mercaptopurine and 5-fluorouracil did not significantly affect the incorporation of lysine into protein, although a small but significant reduction in lysine incorporation was produced by infusion of actinomycin D at 20 mug/kg per hr.5. Development of tolerance to the analgesic effects of morphine was also reduced by cycloheximide and puromycin. These drugs markedly reduced the incorporation of lysine into brain protein. Puromycin and low doses of cycloheximide (50 mug/kg per hr) did not significantly affect RNA synthesis as measured by orotic acid incorporation, but RNA synthesis was clearly reduced by administration of cycloheximide at 200 mug/kg per hr.6. These results support the hypothesis that the synthesis of new RNA and protein in the brain is an essential feature of the development of tolerance to morphine in rats.

Animals↗